Risk factor analysis of lymph node metastasis in endometrial carcinoma combined with molecular types / 中华妇产科杂志

Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.

Clinical and immunological characteristics of 88 cases of overlap myositis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical and immunological characteristics of overlap myositis (OM) patients.@*METHODS@#The data of 368 patients with idiopathic inflammatory myopathies (IIMs) admitted to Peking University People's Hospital from January 2004 to August 2020 were analyzed retrospectively, including demographic characteristics, clinical characteristics (including fever, Gottron' s sign/papules, Heliotrope rash, V-sign, Shawl sign, Mechanic' s hands, skin ulceration, periungual erythema, subcutaneous calcinosis, dysphagia, myalgia, myasthenia, arthritis, Raynaud' s phenomenon, interstitial lung disease, pulmonary hypertension and myocardial involvement), laboratory characteristics, immunological characteristics [including antinuclear antibodies, rheumatoid factors, myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs)] and survival. The clinical and immunological characteristics and prognostic differences of OM and non-OM were compared. The Kaplan-Meier and Log Rank methods were used to analyze the survival.@*RESULTS@#A total of 368 patients were included. 23.9% (88/368) of IIMs patients were OM patients. Among the 88 OM patients, 85.2% (75/88) of them were female, and the median interval between disease onset and diagnosis was 13.5 months. The incidence of overlapped connective tissue diseases in the OM patients was dermatomyositis (DM) in 60.2%, polymyositis (PM) in 3.4%, immune-mediated necrotizing myopathy (IMNM) in 2.3% and anti-synthetase syndrome (ASS) in 34.1%. Compared with the non-OM patients, the proportion of the females in the OM patients was higher (85.2% vs. 72.1%, P=0.016), the OM patients had longer disease duration [13.5(4.5, 48.0) months vs. 4.0(2.0, 12.0) months, P < 0.001]. As for clinical characteristics, compared with the non-OM patients, the incidence of V-sign (25.0% vs. 44.6%, P=0.001) and periungual erythema (8.0% vs. 19.6%, P=0.013) were lower; the incidence of Raynaud's phenomenon (14.8% vs. 1.8%, P < 0.001), interstitial pneumonia (88.6% vs. 72.1%, P=0.001), pulmonary hypertension (22.7% vs. 7.5%, P < 0.001) and myocardial involvement (18.2% vs. 9.3%, P=0.033) were higher. As for immunological characteristics, compared with the non-OM patients, the incidence of elevated aspartate aminotransferase (AST) (31.8% vs. 45.0%, P=0.035) was lower and elevated C-reactive protein (CRP) (58.0% vs. 44.6%, P=0.037) was higher; the positive rates of antinuclear antibodies (ANA) (85.1% vs. 63.4%, P=0.001) and rheumatoid factors (RF) (40.2% vs. 17.8%, P < 0.001) and anti-Ro-52 (71.6% vs. 56.1%, P=0.038) in serum were higher. There was no significant difference in the survival between the OM patients and non-OM patients.@*CONCLUSION@#Pulmonary hypertension and myocardial involvement were frequently observed in OM.

Analysis of the clinical features and misdiagnosis reasons of 17 patients misdiagnosed with IgG4-related disease / 北京大学学报(医学版)

OBJECTIVE@#To summarize the clinical characteristics of patients misdiagnosed with IgG4-related disease, to analyze the reasons of misdiagnosis and to improve the clinical recognition of the disease.@*METHODS@#The general data, clinical manifestations, laboratory examination results and pathological features of 17 patients with IgG4-related diseases misdiagnosed outside the hospital were retrospectively analyzed.@*RESULTS@#Among the 17 patients, there were 9 males and 8 females with a median age of 45 years, and the median time from onset to diagnosis was 12 months. Most patients' initial admission department was not rheumatology or immunology department. Six of the 17 patients were eventually diagnosed with lymphoproliferative disease, 4 with autoimmune disease, and 2 with infectious disease, Rosai Doffman disease, desmofibromatosis, highly differentiated mucoepidermoid carcinoma of the bottom of the mouth, hypereosinophilic syndrome, asthma and allergic rhinitis in 1 case each. The typical sites of IgG4-related disease were involved in 14 patients, including 6 cases of parotid gland, 2 cases of submandibular gland, 3 cases of pancreas and 2 cases of retroperitoneal lesions. Serum IgG4 was elevated in 10 patients, serum IgG4/IgG value was higher than 10% in 7 patients, serum IgE was increased in 7 patients, complement was decreased in 4 patients, and eosinophilic granulocytes were increased in 3 patients. Pathological biopsy was performed in 15 patients, and infiltration of lymphocyte was observed in 10 patients, IgG4+ plasma cells were present in 5 patients, the ratio of IgG4+ plasma cells to IgG+ plasma cells was less than 40% in 4 patients and greater than 40% in 1 patient. However, none of the 15 patients had the storiform pattern of fibrosis and obliterative phlebitis.@*CONCLUSION@#A variety of diseases can perform as IgG4-related disease witih typical sites involved, elevated serum IgG4, even can be characterized by pathological IgG4+ plasma cells infiltration. Physicians should pay attention to the differential diagnosis and comprehensively evaluate the patient's clinical manifestations, and laboratory results. Timely and even repeated pathological biopsy is also needed for definite diagnosis.

Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer.</p><p><b>METHODS</b>PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined.</p><p><b>RESULTS</b>HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins.</p><p><b>CONCLUSION</b>HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.</p>

Age correlates with Gleason score in patients with prostate adenocarcinoma / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between age and Gleason score (GS) in patients with prostate adenocarcinoma.</p><p><b>METHODS</b>This study included 674 patients with pathologically confirmed prostate adenocarcinoma. We determined the GS, primary grade, and secondary grade of the cases, and compared them among different age groups.</p><p><b>RESULTS</b>The mean age of the patients was (70.22 ± 8.26) yr, ranging from 25 to 96 years, (69.06 ± 8.35) yr in those with GS 6, (70.55 ± 8.16) yr in GS 7, (70.99 ± 6.54) yr in GS 8, (71.56 ± 9.18) yr in GS 9, and (72.79 ± 11.36) in GS 10. The mean GS, primary grade, and secondary grade were 7.08 ± 1.09, 3.54 ± 0.72, and 3.53 ± 0.66, respectively, and the mean GSs in the < 60 yr, 60-69 yr, 70-79 yr, and ≥ 80 yr groups were 6.86 ± 1.10, 6.99 ± 1.10, 7.08 ± 1.04, and 7.38 ± 1.23, respectively. Those with GS 6, 7, and ≥ 8 accounted for 37.7%, 34.3%, and 28.0%, respectively. The patients aged < 60, 60-69, 70-79, and ≥ 80 years constituted 10.5% (71/674), 30.6% (206/674), 47.6% (321/674), and 11.3% (76/674), respectively. The age of the patients was significantly correlated with GS (r2 = 0.013, P = 0.003) and the primary grade (r2 = 0.014, P = 0.002), but not the secondary grade (r2 = 0.005, P = 0.055).</p><p><b>CONCLUSION</b>Of the prostate adenocarcinoma patients, those aged ≥ 70 years form a larger proportion, and those with GS ≥ 7 comprise a higher percentage. The age of the patient is correlated with Gleason score but has a limited value in its prediction.</p>

Basic features of the ISUP prostate carcinoma Gleason grading system: a preliminary analysis / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the basic features of the prostate carcinoma Gleason grading system of the International Society of Urological Pathology (ISUP).</p><p><b>METHODS</b>We analyzed the means and proportions of the Gleason score (GS), primary grade (PG), secondary grade (SG) and third grade (TG) of 667 cases of prostate carcinoma.</p><p><b>RESULTS</b>The means of GS, PG, SG and TG were 7.06 +/- 1.10, 3.53 +/- 0.66, 3.53 +/- 0.72 and 4.30 +/- 0.96, respectively. The cases with GS 5, 6, 7, 8, 9 and 10 accounted for 0.4% (3/677), 37.2% (252/677), 34.4% (233/677), 13.7% (93/677), 12.0% (81/677) and 2.2% (15/677), respectively; those with GS < or = 6 and > or = 7 constituted 37.7% (255/677) and 62.3% (422/677); those with GS3 + 3, 4 + 3 and 3 + 4 made up 37.2% (252/677), 19.2% (130/677) and 15.2% (103/677); and the TG cases held 10.3% (70/677), including 30.0% (21/70) of grade 3, 10% (7/70) of grade 4 and 60.0% (42/70) of grade 5.</p><p><b>CONCLUSION</b>Our study showed a high proportion of GS, a low proportion of GS < or = 6, and a high proportion of GS > or = 7 in the ISUP prostate carcinoma Gleason grading system. TG of GS needs to be further understood.</p>

Impact of multidisciplinary team working on the management of colorectal cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline. Colorectal cancer multidisciplinary team (MDT) working model is recommended by UK and other countries, but there is little information on the impact of MDT working on management of colorectal cancer in China. The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.</p><p><b>METHODS</b>A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery, the pre-MDT cohort include 297 patients, recruited from January 1999 to November 2002, and the MDT cohort had 298 patients enrolled from December 2002 to September 2006. Information recorded included: TNM stage from histological reports, degree of differentiation, the number of examined lymph nodes and CT TNM staging performed or not, and its accuracy, including local and distant recurrence.</p><p><b>RESULTS</b>The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group. CT TNM staging was more accurate in the MDT group compared to the pre-MDT group (P = 0.044). The rate of tumor recurrence in the MDT group was lower than pre-MDT group (log-rank test, P < 0.001). Multivariate analysis revealed that age (P = 0.001), management after inception of the MDT (P = 0.002), degree of differentiation (P = 0.003), number of examined lymph nodes (P = 0.002), and TNM stage (P = 0.000) were important factors that independently influence overall survival.</p><p><b>CONCLUSIONS</b>The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients. MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis, evidence-based decision making, and optimal treatment planning.</p>

Clinicopathologic study of 40 cases of mediastinal tumours of haematopoietic and lymphoid tissues / 中华病理学杂志

<p><b>OBJECTIVE</b>To study clinical and histopathological features, and diagnosis of mediastinal tumours of haematopoietic and lymphoid tissues (MTHL).</p><p><b>METHODS</b>Forty cases of MTHL were analyzed for clinicopathology by microscopy and immunohistochemical staining and in situ hybridization, according to the updated 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.</p><p><b>RESULTS</b>In 40 cases of MTHL, there were 20 males and 20 females. The ratio of male/female was 1:1. The mean age was 31.8 years and median age was 29 years (range, 12 - 70 years).Superior vena cava syndrome was observed in 28 cases. The specimens of 4 cases were obtained by lumpectomy, whereas 36 cases by biopsy (25 cases by thoracoscopy, 1 by core needle aspiration). Twenty cases lay in anterior mediastinum, and 2 in posterior, 1 in superior, 8 in anterior and superior, 2 in posterior and superior, 2 in anterior and middle, 1 in middle and anterior mediastinum.Frozen section were performed in 28 cases, and 17 cases were diagnosed as tumours of haematopoietic and lymphoid tissues (consistency ratio was 60.7%). Twelve cases were classical Hodgkin lymphomas (cHL) (8 were nodular sclerosis subtype, and 3 were mixed cellarity, 1 was lymphocyte-rich subtype), and 10 were primary mediastinal (thymic) large B cell lymphoma (PMBCL), 10 were precursor lymphocyte neoplasm [8 were T lymphoblastic leukemia/lymphomas (T-LBL), 2 were B-LBL], 1 was MALT lymphoma, 1 was composite lymphoma (PMBCL and cHL), 2 were myeloid sarcomas, 4 were gray zone lymphomas (GZL) (3 had morphology reminiscent of cHL, and 1 of DLBCL, all cases were positive for CD20, PAX5, CD30 and CD15).EBER were detected in 11 cases by in situ hybridization, 2 of which were positive (18.2%), and the 2 positive cases were cHL.</p><p><b>CONCLUSIONS</b>MTHLs occur predominantly in adolescents and young adults, mainly present as superior vena cava syndrome and anterior mediasinal masses. cHL, PMBCL, T-LBL were the most common MTHLs.GZLs mainly occur in young adults, those whose morphology reminiscent of cHL, immunohistochemistry reminiscent of PMBCL, and vice versa. Thoracoscopy, frozen section and a suitable panel of antibodies were practical approaches to MTHL.</p>

Morphologic changes of fallopian tubal epithelium in ovarian serous tumors / 中华病理学杂志

<p><b>OBJECTIVES</b>To study the morphologic changes of fallopian tubal epithelium in patients with ovarian serous epithelial tumors and to explore the relationship between the tubal epithelial changes and tumorigenesis of serous ovarian carcinoma.</p><p><b>METHODS</b>The fallopian tubes in 79 cases of high-grade serous ovarian carcinoma, 12 cases of low-grade serous ovarian carcinoma, 16 cases of serous borderline ovarian tumor and 11 cases of non-ovarian benign tumors were serially examined under light microscope. Immunohistochemical study with EnVision method was used to detect the expression of p53 and bcl-2 protein in the fallopian tubal epithelium in all cases. The occurrences of secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC) and serous invasive carcinoma were analyzed.</p><p><b>RESULTS</b>SCOUT in tubal epithelium was observed in 60.8% (48/79) of the high-grade serous carcinoma group, 4/12 of the low-grade serous carcinoma group, 3/16 of the serous borderline tumor group and 2/11 of the non-ovarian benign tumor group (P = 0.001). P53 signature, STIC and serous invasive carcinoma occurred only in the fallopian tubal epithelium of patients with high-grade serous ovarian carcinoma, with the positive rates being 29.1% (23/79), 15.2% (12/79) and 44.3% (35/79), respectively. Of the 23 cases with p53 signature, 17 cases had solitary lesion and 6 cases involved more than two sites. A total of 33 p53 signature positive foci were found, with 22 foci located at fimbria and 11 at ampulla. Bcl-2 expression was demonstrated in 90.9% of those foci (30/33). Of the 12 patients with STIC, 7 cases were solitary and 5 cases involved more than two sites. A total of 18 STIC foci were found, with 16 foci located at fimbria and 2 at ampulla. All of them were positive for bcl-2.</p><p><b>CONCLUSIONS</b>SCOUT is found in fallopian tubal epithelium in patients with serous ovarian epithelial tumors, especially high-grade serious carcinoma. On the other hand, p53 signature, STIC and invasive serous carcinoma of tubal epithelium are observed only in patients with high-grade serous ovarian carcinoma, with a predilection of fimbrial involvement. Correlation exists between SCOUT, p53 signature, STIC and high-grade serous ovarian carcinomas. Bcl-2 and p53 immunostaining is helpful for demonstrating such lesions.</p>

Perivascular epithelioid cell tumor of urinary system: a clinicopathologic analysis of 21 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of perivascular epithelioid cell tumors (PEComas) occurring in the urinary system.</p><p><b>METHODS</b>The clinicopathologic features of 21 cases of PEComa from September 2002 to September 2010 occurring in the urinary system were retrospectively reviewed. Immunohistochemical study for HMB 45, S-100 protein, smooth muscle actin, desmin, Melan A and Ki-67 was carried out.</p><p><b>RESULTS</b>Amongst the 21 cases studied, there were 5 males and 16 females. The age of patients ranged from 16 to 76 years (median = 51.3 years). Twenty cases occurred in the kidney and 1 in the bladder. The predominant histopathologic subtype of renal PEComas was classic type (10/20), followed by epithelioid type (5/20), smooth muscle type (3/20), inflammatory type (1/20) and sclerosing type (1/20). Immunohistochemical study showed that HMB 45 and smooth muscle actin were positive in 95.2% (20/21) and 80.9% (17/21) cases, respectively. Melan A, desmin and S-100 protein were expressed in 71.4% (15/21), 61.9% (13/21) and 33.3% (7/21) cases, respectively. The mean proliferative index was 1.29% (range = 0 to 5%). HMB 45 and Melan A were expressed in all of the 5 cases of epithelioid PEComas, whereas smooth muscle actin and desmin were only expressed in one of them. There was no significant difference between epithelioid PEComas and non-epithelioid PEComas in the expression of HMB 45, Melan A, smooth muscle actin and desmin. Positive staining for HMB 45 and smooth muscle actin was demonstrated in the case of bladder PEComa.</p><p><b>CONCLUSIONS</b>PEComas of the urinary system predominantly affect the kidney. Epithelioid renal PEComas and bladder PEComa are relatively rare and have unique pathologic features. It is necessary to distinguish PEComas from other malignant tumors. Immunohistochemical study for HMB 45, Melan A and smooth muscle actin is helpful for confirmation of diagnosis.</p>

Post-transplant lymphoproliferative disorder: a clinicopathologic study of 15 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD).</p><p><b>METHODS</b>The clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues.</p><p><b>RESULTS</b>Amongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease.</p><p><b>CONCLUSIONS</b>The diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.</p>

Expression and promotor methylation of p73 gene in ovarian epithelial tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression and promoter methylation status of p73 gene in ovarian epithelial tumors and their clinicopathological correlations.</p><p><b>METHODS</b>Tissue microarrays (TMA) consisting of 68 ovarian cancers, 37 ovarian borderline tumors and 21 ovarian benign tumors were constructed. p73 expression was detected by immunohistochemistry (EnVision method). Fresh-frozen tissue samples from 13 cases of ovarian carcinomas and 5 cases of borderline tumors were evaluated for the presence of p73 promoter methylation using bisulfite sequencing.</p><p><b>RESULTS</b>Overall, 92.6% (63/68) ovarian carcinomas expressed p73, with a mean value of 32% (percentage of p73 positive cells in the tumor). The mean value of p73 expression rate (40%) in serous carcinoma (26/26) was higher than those of other cancer types (P = 0.006). The mean value of p73 expression rate (40%) in type II ovarian carcinoma was significantly higher than that in type I ovarian carcinoma (24%, P = 0.010). The expression of p73 was not associated with FIGO stage and histological grade (both P > 0.05). The mean values of p73 expression in ovarian borderline tumor (30/37) and benign tumor (12/21) were 16% and 15%, respectively. Of the two groups, the mean value of p73 expression rate in serous type was higher than that in mucous type (P = 0.003, P = 0.026). Ovarian carcinomas had a higher level of p73 expression than borderline tumors and benign tumors (both P < 0.05), while that between ovarian borderline tumors and benign tumors had no statistical difference (P > 0.05). Among serous tumors (49/53), the mean value of p73 expression in the carcinoma group (26/26) was significantly higher than those in the borderline tumor group (12/14) and benign tumor group (11/13; P = 0.024 and P = 0.002, respectively), while that between borderline tumor group and benign tumor group had no statistical difference (P = 0.428). Among mucous tumors (15/27), the mean value of p73 expression in carcinoma group (6/7) was higher than that in benign tumor group (1/8; P = 0.032). No statistical difference of p73 expression was seen between the carcinoma group and ovarian borderline tumor group (8/12) and between the borderline tumor group and benign tumor group (P = 0.234, P = 0.201, respectively). p73 promotor methylation was found in 8 of 13 cases of carcinomas but at different methylation levels with a mean value of 8.0%. Two of 5 ovarian borderline tumors showed detectable p73 promotor methylation with a mean value of 9.0%. Compared with the borderline tumors, ovarian carcinomas showed a similar p73 methylation level (P > 0.05). The p73 methylation level in ovarian carcinomas was not associated with histological type, pathogenetic type, histological grade and FIGO stage (all P > 0.05).</p><p><b>CONCLUSIONS</b>Most of ovarian epithelial tumors express p73 protein with mean values higher in ovarian carcinomas than those in the borderline and benign tumors. Ovarian serous carcinomas have the highest expression level of p73. A simple linear correlation does not exist between the promoter methylation and protein expression of p73.</p>

Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement / 癌症

Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase the resectability of tumors, has recently evolved as a treatment for locally advanced cervical cancer. NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer. To further assess the effects of NACT on surgery and the pathologic characteristics of cervical cancer, we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or without NACT at the People's Hospital of Peking University between January 2006 and December 2010. Of 110 patients, 68 underwent platinum-based NACT prior to surgery (NACT group) and 42 underwent primary surgery treatment (PST group). Our results showed 48 of 68 (70.6%) patients achieved a complete response or partial response to NACT. Estimated blood loss, operation time, and number of removed lymph nodes during surgery, as well as complication rates during and after surgery were not significantly different between the NACT group and the PST group. The rates of deep stromal invasion, positive parametria, positive surgical vaginal margins, and lymph node metastasis were not significantly different between the two groups. However, the rate of lymph-vascular space involvement (LVSI) was significantly lower in the NACT group than in the PST group (P = 0.021). In addition, the response rate of NACT was significantly higher in the patients with chemotherapeutic drugs administrated via artery than via vein. Our results suggest that NACT is a safe and effective treatment for locally advanced cervical cancer and significantly decreases the rate of LVSI.

Diffuse pulmonary lymphangiomatosis: a case report with literature review / 中华医学杂志(英文版)

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease that is characterized by diffuse proliferation of abnormal pulmonary lymphatic channels. DPL occurs mostly in children and young adults and often undergoes a progressive clinical course, eventually causing deterioration of the lung. Both the clinical diagnosis and treatment of DPL remain a challenge. Here, we report a case of DPL in a 53-year-old Chinese woman with comprehensive investigations including pulmonary function tests, computer tomography (CT), bronchoscopy and histological examination of the lung biopsy, and review the literature.

Immunohistochemistry of p57 and p53 protein in differential diagnosis of hydropic abortion, partial and complete hydatidiform mole / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole.</p><p><b>METHODS</b>Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20).</p><p><b>RESULTS</b>The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05).</p><p><b>CONCLUSIONS</b>Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.</p>

Expression of PLAC1/CP1 genes in primary colorectal carcinoma and its clinical significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression and significance of PLAC1/CP1 genes in patients with primary colorectal carcinoma.</p><p><b>METHODS</b>The expression of PLAC1/CP1 genes in 97 cases of colorectal carcinoma was studied using tissue chip technology and immunohistochemistry.</p><p><b>RESULTS</b>The rate of PLAC1/CP1 proteins expression in the cases studied was 56.7% (55/97), with 27.8% (27/97) being nuclear staining and 43.3% (42/97) being cytoplasmic staining. The percentage of expression was higher in women than in men (χ(2) = 6.567, P = 0.010). The expression in poorly differentiated colorectal carcinoma was significantly higher than that in the well or moderately differentiated carcinoma (χ(2) = 8.321, P = 0.016). The expression was also significantly higher in stage TNM III or IV tumors than in stage TNM I or II tumors (χ(2) = 18.726, P = 0.000). The rate was higher in cases with lymph node metastasis than in those with negative lymph nodes (χ(2) = 17.407, P = 0.000), and was higher as the number of metastasis increasing (χ(2) = 22.632, P = 0.000).</p><p><b>CONCLUSION</b>The expression of PLAC1/CP1 genes correlates with various clinical and pathologic parameters. It carries prognostic significance and may represent a potential target for immunotherapy.</p>

Expression of folate receptor alpha in ovarian epithelial tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>to investigate the expression of folate receptor(FR)α in ovarian epithelial tumors and its clinopathological significance.</p><p><b>METHODS</b>tissue microarrays (TMAs) were constructed from 86 epithelial ovarian cancers and 29 borderline ovarian tumors, followed by the FRα expression evaluation by immunohistochemistry. FRα mRNA expression was investigated by quantitative real-time PCR using fresh-frozen tissues from 40 cases of ovarian carcinoma and 14 cases of borderline tumor. FRα expression levels in ovarian tumors were also analyzed in correlation with tumor morphology, pathogenesis and FIGO stage.</p><p><b>RESULTS</b>FRα expression was detected in 40 of 86 (46.5%) of ovarian cancers, with the highest rate of expression observed in serous carcinomas (62.7%, 32/51) compared with that of the other cancer types (P = 0.000). Depending on pathogenesis type, FRα expressions in type II ovarian carcinomas were significantly higher than those in type I ovarian carcinomas (P = 0.001). Ovarian carcinomas had a tendency to express higher FRα than the borderline tumors (46.5% vs 27.6%), although statistically not significant (P = 0.074). FRα expressions in ovarian carcinomas showed no correlation with the FIGO stage (P = 0.498). However, real-time PCR showed that FRα mRNA levels were significantly higher in ovarian carcinomas compared with that of the borderline tumors (P = 0.000) and also higher in serous ovarian borderline tumors compared with mucinous type (P = 0.007).</p><p><b>CONCLUSION</b>higher level of FRα expression occurs frequently in ovarian epithelial tumors, especially in carcinomas and ovarian serous tumors.</p>

Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma (PPC).</p><p><b>METHODS</b>Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2alpha, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis.</p><p><b>RESULTS</b>There were 15 cases of primary peritoneal serous papillary carcinoma (PPSPC), 6 cases of mixed epithelial carcinoma (MEC) and 3 cases of malignant mixed Mullerian tumor (MMMT). All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen (paclitaxel-cisplatin or carboplatin) and 7 patients received the PAC regimen (cisplatin-doxorubicin-cyclophosphamide). The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2alpha and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT (44 months vs 13 months, P<0.05), also between patients receiving TP combination and those receiving the PAC regimen (75 months vs 28 months, P<0.05). Another significant difference in the median progression-free survival (PFS) was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining (15 months vs 47 months, P<0.05), whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival.</p><p><b>CONCLUSION</b>Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an optimal debulking surgery may not benefit survival. The pathologic subtype, chemotherapy regimen and p53 overexpression were significant prognostic factors.</p>

Analysis of HER2 gene amplification and its protein expression in 165 cases of breast carcinoma: comparison of chromogenic in-situ hybridization and immunohistochemistry / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity and specificity of chromogenic in-situ hybridization (CISH) in detecting HER2 gene amplification in breast carcinomas.</p><p><b>METHODS</b>HER2 oncogene amplification and its protein expression in 165 cases of breast carcinoma were investigated by immunohistochemistry (IHC) and CISH.</p><p><b>RESULTS</b>(1) CISH did not detect HER2 gene amplification in 107 cases of IHC negative tumors and 24 cases of IHC 1+ tumors. (2) CISH identified high copy numbers of HER2 gene amplification in 21/22 (95.5%) cases with IHC 3+. (3) In 12 HIC 2+ cases, CISH identified 3 cases of high copy number amplification, 6 cases of low copy number amplification and 3 cases without amplification.</p><p><b>CONCLUSIONS</b>HER2 gene amplification detection by CISH is highly sensitive and has a high concordance with IHC detection of the protein expression. It is concluded that CISH is a tool to evaluate HER2 gene status in breast cancer and can be an implement in conventional pathology laboratories.</p>

Clinicopathologic analysis of 141 cases of metastatic carcinoma in bone / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of metastatic carcinoma in bone and to evaluate the role of immunohistochemistry in delineation of possible primary sites.</p><p><b>METHODS</b>One hundred and forty-one cases of metastatic carcinoma in bone encountered during the period from 1998 to 2004 in People's Hospital, Peking University, were reviewed retrospectively. The clinical information, radiographic features and pathologic findings were analyzed. Immunohistochemical study for antigens including cytokeratins, prostatic specific antigen, thyroglobulin, thyroid transcription factor 1 and gross cystic disease fluid protein 15, was performed in 51 cases possessing skeletal metastasis with unknown primary.</p><p><b>RESULTS</b>Skeletal metastasis occurred more commonly in males (male to female ratio = 1.7:1). The age of patients ranged from 23 to 86 years (mean age = 56.5). The presenting symptoms included pain and dysfunction in the affected bones. The locations of skeletal metastasis were as follows: spine (58), pelvic bone (46), long bone (34) and others (3). Twenty-three cases harbored multiple bony lesions. Radiographically, 99 cases (70.2%) of skeletal metastasis were detected by X-rays, including 85 cases (85.9%) showing lytic changes. The primary sites of the tumor could be determined by clinicopathologic correlation in 90 cases (63.8%) and were unknown in the remaining 51 cases. Upon immunohistochemical study, the primary sites were determined in another 40 cases. Overall, the primary sites were identified in 130 cases (92.2%), which included lung (37), female genital system and breast (25), kidney (18), gastrointestinal system (17), liver (12), thyroid (11), prostate (7), bladder (2) and skin (1).</p><p><b>CONCLUSIONS</b>Skeletal metastasis occurs more often in elderly males. Axial bones (spine and pelvis) are usually affected. Lung and female genital system are frequent the primary sites. Immunohistochemical study is useful in cases with occult primary.</p>