Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis.

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.

Association of Self-Reported Sleep Characteristics and Hip Fracture: Observational and Mendelian Randomization Studies.

Previous observational studies on the relationship between sleep characteristics and fracture have yielded contradictory results. The goal of this study was to replicate the findings in a large longitudinal cohort and then conduct a Mendelian randomization (MR) analysis to infer the causality between sleep behaviors and fracture risk. Based on data from the China Health and Retirement Longitudinal Study (CHARLS) including 17,708 participants, we found that individuals with short sleep duration (<5 h) (OR [odds ratio] = 1.62, 95% CI: 1.07-2.44) or restless sleep (OR = 1.55, 95% CI: 1.10-2.19) have a higher risk of hip fracture. A U-shaped relationship between nighttime sleep duration and hip fracture risk (p-nonlinear = 0.01) was observed using restricted cubic spline regression analysis. Through joint effect analysis, we found that participants with short sleep duration (<5 h) combined with midday napping could significantly decrease hip fracture incidence. We further inferred the causal relationship between self-reported sleep behaviors and hip fracture using the MR approach. Among four sleep phenotypic parameters (sleep duration, daytime napping, chronotype, and insomnia), we found a modest causal relationship between sleep duration and fracture (OR = 0.69, 95% CI: 0.48 to 0.99, p = 0.04). However, no causal relationship was observed for other sleep traits. In conclusion, our findings suggest that short sleep duration has a potential detrimental effect on hip fracture. Improving sleep patterns is of significance for developing hip fracture preventive strategies in the middle-aged and the elderly populations.

Exploring Strategies for Improving Green Open Spaces in Old Downtown Residential Communities from the Perspective of Public Health to Enhance the Health and Well-Being of the Aged.

Based on the trend of global aging, people are paying more and more attention to the health of the elderly and the improvement of green open spaces. However, few studies have focused on strategies to improve green spaces in response to this trend. Especially, with the outbreak of COVID-19, an urgent need to develop a sustainable system strategy to improve the health of the elderly in residential communities in old districts has emerged. Traditional improvement strategies based on current situation evaluation often focus on the most prominent practical problems. Therefore, the objective of this study was to provide theoretical research and practical improvement strategies for green open spaces in old downtown residential communities to improve the health and well-being of the elderly. In response to this problem, this research proposes an alternative method based on causality (FDM-DANP-mV model), by extracting 23 green open space elements that affect the health of the elderly and dividing them into three dimensions, to form a preliminary evaluation framework. On this basis, the more effective and feasible standard elements are screened out, and the influence relationship behind the elements is clarified. Then, the sustainable development strategy is systematically discussed in three practical cases. This allows for the analysis of the present situation to not only identify the current significant problems but also to capture the source of the influence behind the real problems based on the clarification of the dominant influence relationship. The actual value of this study is to provide a key design decision basis for the improvement of the green open spaces in old downtown residential communities, aiming at avoiding waste to the greatest extent under the premise of limited resources and gradually promoting the improvement of the urban built environment to promote the health and well-being of the elderly.

Hormone receptors analysis in Chinese patients with dermatofibrosarcoma protuberans.

BACKGROUND AND OBJECTIVES: Dermatofibrosarcoma protuberans (DFSP) is a relatively rare skin tumor. Clinical observations indicated that DFSP has a more aggressive behavior during pregnancy, which suggest there might be a hormonal influence on this tumor. We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) in DFSP patients. METHODS: In our present case series, patients with histopathological-confirmed DFSP at a single institution were identified. The clinical, pathological, and immunohistochemical data were gathered for each patient. Expression of ER and PR were determined on formalin-fixed, paraffin-embedded tissue sections using immunohistochemistry. Some objective clinical and pathological indicators were then selected to compare between ER and PR status. RESULTS: Immunoreactivity revealed none of these tumors stained positively for ER, while eight tumors (28.6%) stained positively for PR. There was a statistically significant difference in the distribution of tumor location between the PR-positive/negative groups. CONCLUSIONS: This finding suggests that progesterone may have potential effects in growth of DFSPs. Further studies are needed to fully address this question.

Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer.

AIM: To detect the expression of threonine and tyrosine kinase (TTK) in gallbladder cancer (GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical prognosis. METHODS: A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTK expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of TTK in the cytoplasm and nucleus was scored separately to achieve respective H-score values. The correlations between TTK expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. RESULTS: In both the nucleus and cytoplasm, the expression of TTK in tumor tissues was significantly lower than that in normal tissues (P < 0.001 and P = 0.026, respectively). Using the median H-score as the cutoff value, it was discovered that, GBC patients with higher levels of TTK expression in the nucleus, but not the cytoplasm, had favorable overall survival (P < 0.001), and it was still statistically meaningful in Cox regression analysis. Further investigation indicated that there were close negative correlations between TTK expression and tumor differentiation (P = 0.041), CA 19-9 levels (P = 0.016), T stage (P < 0.001), nodal involvement (P < 0.001), distant metastasis (P = 0.024) and TNM stage (P < 0.001). CONCLUSION: The expression of TTK in GBC is lower than that in normal tissues. Higher levels of TTK expression in GBC are concomitant with longer overall survival. TTK is a favorable prognostic biomarker for patients with GBC.

Differences between low and high grade fetal adenocarcinoma of the lung: a clinicopathological and molecular study.

BACKGROUND: Fetal adenocarcinoma of the lung (FLAC) is a rare entity of lung cancer. It is classified into low-grade fetal adenocarcinoma (L-FLAC) and high-grade fetal adenocarcinoma (H-FLAC). We aim to report the clinicopathological and molecular features of FLAC in Chinese patients. METHODS: FLACs were screened from a consecutive lung adenocarcinoma series comprising 920 cases. The clinicopathological features L-FLAC and H-FLAC were retrospectively reviewed via immunohistochemical study and mutation analysis. RESULTS: Three L-FLAC and five H-FLAC cases were identified. L-FLAC mainly occurred in young patients and was predominantly in stage I upon diagnosis and conferred favorable outcomes. L-FLAC tumors were characterized by the glycogen-rich columnar cells lining the complex glandular structures, with low nuclear atypia, morule formation, and mainly nuclear- and cytoplasmic-localized ß-catenin expression. In contrast, H-FLAC predominantly occurred in elderly men with a history of smoking. The stage of H-FLAC was often advanced at presentation and had a poor prognosis. H-FLAC tumors exhibited more prominent atypia of the nucleus, the absence of morule formation, and largely membrane-localized ß-catenin. All 5 H-FLACs were immunohistochemically characterized by overexpression of the p53 protein; the L-FLAC tumors were negative for p53. Two cases of H-FLAC were positive for AFP. No Her-2 or ALK-D5F3 overexpression was observed in any of the tumors. EGFR L858R point mutation was identified in one of the H-FLAC cases. EGFR T790M mutation was detected in one of the L-FLAC cases. No mutations in KRAS, PIK3CA or BRAF were detected. CONCLUSIONS: L-FLAC and H-FLAC exhibited distinctive clinicopathological, immunophenotypic and molecular features with potential prognostic value.

[Pulmonary neuroendocrine cell hyperplasia and tumorlets in bronchiectasis: a clinicopathologic study of 22 cases with review of literature].

OBJECTIVE: To study the clinical and pathological features of pulmonary neuroendocrine cell hyperplasia and tumorlets with bronchiectasis. METHODS: Both the clinicopathologic changes and immunohistochemical findings were examined with microscopy and EnVision method in 22 cases of pulmonary neuroendocrine cell hyperplasia and tumorlets. RESULTS: The average age of the 22 patients was 53 years, with a male to female ratio of 9:13. On macroscopic examination the lungs showed bronchiectasis; one case was accompanied by gray-white, soft nodules (diameter < 5 mm). Microscopy of the HE sections showed the basic pathologic change was bronchiectasis, accompanied by neuroendocrine cell hyperplasia and tumorlet formation in the pulmonary parenchyma surrounding the bronchioles, presenting as single nodule (10 patients), or multifocal nodules (12 patients), with average size of 1.6 mm in diameter. No tumor cells were identified in the lymph nodes. Sixteen of 22 patients were disease-free after an average follow-up period of 58 months (17 - 117 months); one patient died suddenly after surgery; and five were loss of follow up. Immunohistologically, the tumor cells were positive for CgA (18/18), Syn (16/16), AE1/AE3 (16/16) , TTF-1 (14/15), and CD56 (14/14), and Ki-67 index was < 2% in 12 cases. CONCLUSIONS: Immunohistological staining for CgA, Syn, CD56, TTF-1 and AE1/AE3 can confirm the diagnosis. Early detection, pulmonary resection and follow-up help prevent the progression of these diseases.

Procalcitonin is a good tool to guide duration of antibiotic therapy in patients with severe acute pancreatitis. A randomized prospective single-center controlled trial.

OBJECTIVE: To investigate the clinical usefulness of procalcitonin (PCT) for guiding duration of antibiotic therapy in patients with severe acute pancreatitis (SAP). METHODS: A total of 71 patients with confirmed severe acute pancreatitis from March 2009 to September 2011 in the Department of Critical Care Medicine of Huizhou Municipal Central Hospital, Guangdong, China were enrolled in this study. Procalcitonin was measured daily by a semi-quantitative immunoassay in the study group. Patients were randomly assigned into 2 groups including a PCT-guided group (study group) and a prophylactic antibiotic therapy (control group). Antibiotic therapy in the study group was not applied until clinical signs and symptoms of infection appeared (PCT value was >0.5ng/ml). We discontinued the antibiotic therapy if clinical signs and symptoms of infection improved and PCT was <0.5ng/ml over 3 days. In the control group, antibiotic therapy was administrated for 2 weeks, or antibiotic therapy was continued because of confirmed infection until clinical signs and symptoms of infection disappeared over 3 days. RESULTS: In the study group (35 patients), the duration of antibiotic therapy and hospitalization was significantly shorter than the control group (36 patients) (10.89+/-2.85 versus 16.06+/-2.48 days, p<0.001, and 16.66+/-4.02 days versus 23.81+/-7.56 days, p<0.001) without negative clinical effects and the cost of hospitalization was significantly lower. CONCLUSION: Procalcitonin is a helpful and safe tool for guiding duration of antibiotic treatment in patients with severe acute pancreatitis.

[Tubulolobular carcinoma of breast: a clinicopathologic study of 8 cases].

OBJECTIVE: To study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC). METHODS: Eight cases of TLC were retrieved from 97 cases of invasive lobular carcinoma between January 2005 and March 2010 in the Peking Union Medical College Hospital. The clinical features and pathologic findings were studied and immunohistochemistry was performed for the expression of ER, PR, HER2, p53, E-cadherin, CK34ßE12 and CK8. RESULTS: Among the breast cancer patients, the incidence of TLC was about 1.0% (8/880). The mean age of the patients was 59 years, with a range of 45 to 79 years. All patients were asymptomatic, with incidental finding of a mass in the breast on health examination. Common findings on sonography included a hypoechoic nodule with irregular shape and spiculated margin. Histologically, the small uniform tumor cells were arranged in a mixed pattern showing single cells, single-cell files or cords, small round to angulated tubules, and infiltrating lobular or targetoid patterns around ducts that were specific for classical invasive lobular carcinoma. Low or intermediate grade intraepithelial neoplasms which had similar cellular morphology with the invasive tumor often appeared in the periphery, including ductal carcinoma in situ, lobular carcinoma in situ and intraductal papillary carcinoma. Immunohistochemistry of the tumor cells showed intense reactivity to ER (7/8) and PR (8/8), but no reactivity to HER2 or p53. Both the tubules and single-cell file or cords expressed E-cadherin (7/8), CK34ßE12 (5/8), and CK8 (8/8) with a uniform staining pattern. All patients underwent modified radical mastectomy and 2/8 patients had metastatic carcinoma in the axillary lymph nodes. Seven patients were followed up for 28 to 75 months and remained well, including one patient that had a new breast mass 60 months after surgery, but had no treatment up to now. CONCLUSIONS: TLC is a rare variant of invasive breast cancer and reveals mixed histologic features of both tubular and lobular carcinoma with common expression of E-cadherin, CK8 and CK34ßE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.

[Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study].

OBJECTIVE: To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis. METHODS: Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies. RESULTS: The age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected. CONCLUSIONS: Pulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature.

[Significance of chemokine receptor CXCR3 expression in breast cancer].

OBJECTIVE: To investigate the expression of CXCR3 and its association with clinicopathologic features in breast carcinoma. METHODS: The expression level of CXCR3 in 18 samples of breast cancer and corresponding normal tissues was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis. Immunohistochemistry was carried out to examine the expression of CXCR3 in 80 breast cancers, 20 fibroadenomas and 15 normal breast tissues. RESULTS: (1) RT-PCR and real-time RT-PCR analysis showed a higher level of CXCR3 in breast cancer tissues than that in the corresponding normal breast tissues (P < 0.05). (2) Immunohistochemistry analysis showed that the positive rate of CXCR3 in breast cancer tissues was significantly higher than that in fibroadenomas and the normal breast tissues (P < 0.05). The expression level of CXCR3 in the lymph node-positive group was higher than that in the lymph node-negative group (P < 0.05). The expression of CXCR3 was positively correlated with the number of lymph nodes involved by metastasis, tumor size and pTNM tumor stage (P < 0.05). CONCLUSIONS: Chemokine receptor CXCR3 was up-regulated in breast cancer, and was associated with the progression of breast cancer. CXCR3 might be a novel molecular marker to predict lymph node metastasis and prognosis of breast cancer.

[Colloid carcinoma of pancreas: a clinicopathologic study of 4 cases].

OBJECTIVE: To study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of colloid carcinoma of the pancreas. METHODS: The clinical findings, morphologic features, immunophenotype and K-ras gene alterations were investigated in 4 cases of pancreatic colloid carcinoma. RESULTS: In the 4 cases of colloid carcinoma of the pancreas, three tumors were located in the head of the pancreas, one was located in the body and tail. The average age was 56.5 years old. The presenting symptom was abdominal pain in 2 cases, increased level of U-GLU in 1 patient, and an accidental finding presented in 1 patient. Grossly, 3 cases were cystic and solid, with mucin in the cyst; 1 case was solid. Microscopically, the colloid carcinoma was characterized by large pools of extracellular mucin, containing neoplastic cells, which were in the pattern of cuboidal, cribriform or irregular clusters, or formed an incomplete lining separating mucin pools from the stroma. Three cases developed from pre-existing pancreatic ductal adenocarcinoma (IPMN), intestinal-type, and 1 from IPMN, pancreatobiliary-type. Immunohistochemical studies showed that MUC2 was positive in 3 cases, and MUC1 in 1 case. K-ras gene mutation was identified in 2 cases, showing a single-amino-acid substitution in codon 12, as Gly12Asp (GGT > GAT) and Gly12Arg (GGT > CGT). CONCLUSIONS: Pancreatic colloid carcinoma is a rare variant of pancreatic ductal adenocarcinoma, which is associated with IPMN and mucinous cystic neoplasms. Positive MUC2 staining and absent MUC1 expression are commonly found, and K-ras gene mutation is occasionally identified in these tumors.

Expression of proteasome immunosubunit in labial glands of patients with primary Sjogren's syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of proteasome immunosubunit low molecular weight polypeptide (LMP)2 and LMP7 in labial glands of patients with primary Sjogren's syndrome patients, and thus explore their role in the diagnosis, differential diagnosis and pathogenesis of primary Sjogren's syndrome (pSS).</p><p><b>METHODS</b>Labial specimens were collected from 40 patients with pSS, 15 patients with connective tissue diseases other than pSS, and 9 healthy controls. The expressions of LMP2 and LMP7 in labial specimens were determined using immunohistochemical approaches and analyzed using semi-quantitative methods. The positive rate of acinar was calculated. After the square arcsine transformation of data, the differences of the positive rate in acinar between LMP2 and LMP7 were compared among three groups. Spearman's rank correlation coefficient was used for analyzing the correlation of clinical manifestations with LMP2 and LMP7 expressions.</p><p><b>RESULTS</b>The expressions of LMP2 and LMP7 within the acinar and ductal epithelial cells were confirmed. Although the LMP2 expression in labial specimens was not significantly different among three groups(P=0.369), the expression of LMP7 was significantly higher in pSS patients compared with patients with connective tissue disease and healthy controls (P<0.01). Only in pSS group, LMP7 was found to be with higher positive rate in acinar than LMP2 (P<0.01). No significant correlation was found between LMP2/LMP7 and clinical manifestations (P>0.05).</p><p><b>CONCLUSION</b>In patients with pSS, the expression of LMP7 (but not LMP2) is up-regulated in labial gland, indicating these two proteins have different genetic regulation mechanisms.</p>

[Infection of human papillomavirus 16/18 DNA in patients with head and neck squamous cell carcinoma and its relationship with expression of Ki-67 and P53 protein].

OBJECTIVE: To detect the infection of human papillomavirus (HPV) 16/18 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expressions of Ki-67 and P53 proteins in tumor tissue. METHOD: The level of HPV 16/18 DNA was measured by real time polymerase chain reaction, and Ki-67 and P53 proteins were measured by immunohistochemistry in tissues from head and neck squamous cell carcinoma. RESULTS: HPV 16/18 DNA was detected in 62.8% of our patients. In each cancer tissue sample, Ki-67 protein was expressed between 2% to 70%. P53 protein was expressed in 46.15% of our patients. No significant relation was found between HPV 16/18 DNA level and sex, smoking, drinking, and tumor clinical stages. However, level of HPV 16/18 DNA was found to have positive relation with tumor pathological grades and negative relation with P53 protein expression. No relation with Ki-67 protein expression was found. CONCLUSION: Head and neck squamous cell carcinoma may be initiated by HPV 16/18 infection and the mechanism in carcinogenesis involves abnormal expression in P53 protein.

[Clinicopathologic study of 7 cases of gastric T-cell lymphoma].

OBJECTIVE: To study the clinicopathologic characteristics of gastric T-cell lymphoma. METHODS: The clinicopathologic features of 7 cases of gastric T-cell lymphoma were retrospectively reviewed. Immunohistochemical study, T-cell receptor gene rearrangement analysis and evaluation of Epstein Barr virus (EBV) status were also performed. RESULTS: The median age at onset of gastric T-cell lymphoma was 45 years. The male-to-female ratio was 6 to 1. The clinical information was available in 6 cases; and one of them had history of persistent diarrhea and 5 had hypoproteinemia. Histologically, 5 cases consisted of large lymphoma cells and the remaining 2 cases showed mainly medium-sized cells. Intraepithelial lymphoma cell infiltration was found in one case. The lymphoma cells of all cases were negative for CD20 and CD79a. CD3 and TIA-1 expression was noted in 6 of the 7 cases. CD5, ßF-1 and CD30 were positive in 4 cases and CD4 was positive in 3 cases. In-situ hybridization for Epstein-Barr virus-encoded RNA was negative. Clonal T-cell receptor gene rearrangement was demonstrated in all cases. CONCLUSION: Gastric T-cell lymphoma is a rare type of malignant lymphoma, with distinctive clinicopathologic characteristics.

[Pulmonary adenocarcinoma with micropapillary pattern: a clinicopathologic and immunohistochemical study].

OBJECTIVE: To study the clinicopathologic characteristics and immunohistochemical profile of lung adenocarcinomas with a micropapillary pattern (MPP). METHODS: Among 135 cases of lung adenocarcinomas, the clinical, histological and immunohistochemical features of 48 cases of lung adenocarcinomas with a micropapillary components (the micropapillary components > or = 10%) were studied. The literature was reviewed. RESULTS: All the 135 cases were resected pulmonary adenocarcinomas. Among 48 cases of lung adenocarcinomas with a micropapillary components, the age of patients ranged from 43 to 85 years (mean = 60.7 years). The male-to-female ratio was 9:7. Histologically, 36 cases of lung adenocarcinomas with the MPP were characterized by small papillary tufts lacking a central fibrovascular core lying freely within alveolar spaces (IA type) or in the clefts of fibrous tissue just like those in MPP breast cancers (IB type). Another type of the micropapillary pattern consisted of 12 cases, the micropapillary tufts floating within cystic spaces lined by tumor cells (II type). In micropapillary pattern-positive cases, lymphatic invasion and lymph node metastasis were identified significantly more frequently than in micropapillary pattern-negative cases (P < 0.01). The percentages of cases positive for various markers were 97.9% (47/48) for E-cadherin, 89.5% (43/48) for beta-catenin, 91.7% (44/48) for Muc-1, 70.8% (34/48) for epidermal growth factor receptor, 35.4% (17/48) for p53, 93.8% (45/48) for Ki-67. The percentages of cases with high expression (including 3+ or 4+) for these markers were 72.3% (34/47) for E-cadherin, 90.7% (39/43) for beta-catenin, 88.6% (39/44) for Muc-1, 52.8% (19/36) for epidermal growth factor receptor, 58.8% (10/17) for p53, 46.7% (16/36) for Ki-67. Adequate clinical follow-up information was available for 36 patients. The mean follow-up time was 21.1 months. Among these, 16 of 36 patients (44.4%) were alive with no evidence of tumor, 12(33.3%) were died, and 8 (22.2%) were alive with tumor. CONCLUSION: Lung adenocarcinomas with the MPP correlates positively with lymphatic invasion and lymph node metastasis, and are likely to have a potential for high malignancy, suggesting a poor prognosis.

[Clinicopathologic study of primary marginal zone B-cell lymphoma of MALT type and lymphoid hyperplasia of lung].

OBJECTIVE: To study the clinicopathologic features, immunohistochemical findings and immunoglobulin heavy chain (IgH) gene rearrangement results of primary pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) and reactive lymphoid hyperplasia. METHODS: Twenty cases, included 13 cases of pulmonary MALToma and 7 cases of pulmonary lymphoid hyperplasia, encountered during the period from 1989 to 2007, were retrospectively analyzed. The samples were paraffin-embedded and stained with hematoxylin and eosin. Immunohistochemical study and semi-nested polymerase chain reaction for IgH gene rearrangement were performed. RESULTS: The 13 cases of primary pulmonary MALToma were composed of a spectrum of lymphoid cells, including lymphocyte-like cells, centrocyte-like cells and mononuclear B cells with plasmacytoid differentiation. They often had diffuse or marginal zone growth patterns. Lymphoid follicles with neoplastic colonization were apparent. The lymphoma cells spread along alveolar septa and bronchovascular bundles. Vascular invasion was noted in 9 cases, pleura involvement in 6 cases and nodal involvement in 2 cases. Lymphoepithelial lesions (LEL) were identified in 9 cases of pulmonary MALToma. Immunohistochemically, the lymphocytes in LEL were CD20-positive and CD3-negative. On the other hand, LEL was also present in 2 of the 7 cases of lymphoid hyperplasia studied, with a mixture of CD20-positive B cells and CD3-negative T cells. Eight of the 9 cases of primary pulmonary MALToma were positive for IgH gene rearrangement, while all of the 7 cases of lymphoid hyperplasia were negative. CONCLUSIONS: Histologically, the cell population of primary pulmonary MALToma is similar to that of extranodal MALToma occurring in other organs. LEL, though commonly observed in pulmonary MALToma, are not specific and can also be seen in cases of reactive lymphoid hyperplasia. The immunophenotype of intraepithelial lymphocytes in pulmonary MALToma and reactive lymphoid hyperplasia is different. The presence of a monotonous population of CD20-positive intraepithelial lymphocytes supports a diagnosis of MALToma. IgH gene rearrangement study is also useful in differentiating both entities.

[Expression of survivin in colorectal adenoma and adenocarcinoma].

OBJECTIVE: To explore the expression of Survivin (SVV) protein in colorectal carcinogenesis and its clinical significance. METHODS Immunohistochemistry staining was performed by two-step EnVision technique for the paraffin sections, which included 90 adenomas, 25 ademomas with high-grade glandular intraepithelial neoplasia, and 108 colorectal adenocarcinomas. RESULTS: Expressions of SVV, P53, and Bcl-2 were observed in tumor cells of the sections. The positive rate of SVV in tubular adenomas, villous adenomas, and tubulovillous adenomas were 30% (12/40), 40.9% (9/22), and 35.8% (10/28), respectively. The positive rate of SVV in tubulovillous adenomas with high-grade glandular intraepithelial neoplasia were 68% (17/25). The positive rate of SVV in carcinomas of stage A, B, and C were 75% (27/36), 81.3% (26/ 32), and 95% (38/40), respectively. SVV expressions among the three types of adenomas without neoplasia were not significantly different (P > 0.05). SVV expression between each type of the above-mentioned ademoma and tubulovillous adenoma with high-grade glandular intraepithelial neoplasia or different Dukes stages of colorectal carcinoma was significantly different (P < 0.05). SVV expressions in adenocarcinomas and adenomas with high grade glandular intraepithelial neoplasia were significantly higher than those in adenomas (P < 0.01). The expressions of P53 and Bcl-2 had no significant difference among them. No association was noted between SVV expression and P53 or Bcl-2 expression (P = 0.487, P = 0. 437). CONCLUSIONS: SVV is abnormally expressed in the early stage of colorectal carcinogenesis, which may be correlated with the carcinogenesis of colorectal ademoma. SVV expression may be useful to distinguish adenocarcinoma from adenoma in colorectal carcinogenesis.

[The significance of Ki-67 antigen expression in the distinction between benign and malignant pheochromocytomas].

OBJECTIVES: To investigate the expression of Ki-67 antigen in benign and malignant pheochromocytomas, and to evaluate whether the expression of Ki-67 antigen could serve as a diagnostic marker for predicting the biological behaviour of these tumors. METHODS: Ki-67 antigen were detected by immunohistochemical technique and image analysis in 57 cases of clinically documented benign and malignant pheochromocytomas were analyzed. Aside from histological study, Ki-67 immunohistochemistry studies were performed to get the Ki-67 index. Statistical analysis was performed between these groups. RESULTS: Ki-67 index was low in benign pheochromocytomas (average 0.98%), and high in malignant pheochromocytomas (average 3.78%). There was statistically significant difference in expressions of Ki-67 antigen between benign and malignant pheochromocytomas. The Ki-67 index of 2 cases in benign pheochromocytomas (5.1%, 2/39) and 10 cases in malignant pheochromocytomas (55.6%, 10/18) was higher than 3%. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of Ki-67 index higher than 3% to diagnosis malignant pheochromocytomas was 82.5%, 55.6%, 94.9%, 83.3% and 82.2%. The follow-ups indicated the survival rate of patients with higher Ki-67 index was lower than those with lower Ki-67 index. CONCLUSIONS: Ki-67 may serve as a useful marker of the biological behavior of tumors, and can provide useful information for prognosis of tumor patients. Immunohistochemical assessment of Ki-67 antigen can be useful in the differential diagnosis of malignant from benign pheochromocytomas. Ki-67 index (> 3%) is a useful marker for distinguishing benign from malignant tumors or for predicting the malignant potential of pheochromocytomas.