Expression of programmed death ligand 1 in lung adenocarcinoma and its significance / 肿瘤研究与临床

Objective To investigate the expression of programmed death ligand 1 (PD-L1) in lung adenocarcinoma tissues and its correlation with clinicopathological features of patients. Methods A total of 141 paraffin-embedded specimens of patients with newly diagnosed lung adenocarcinoma by pathology from January to August 2018 in the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School were collected. The expression of PD-L1 in the tumor cells (TC) and tumor-infiltrating immune cells (IC) were detected by immunohistochemistry EnVision staining. Based on the percentage of expression, PD-L1 in TC and IC were divided into TC3 (≥50％), TC2 (≥5％ and <50％), TC1 (≥1％ and <5％), and TC0 (<1％); IC3 (≥10％), IC2 (≥5％ and <10％), IC1 (≥1％ and <5％), and IC0 (<1％). Results PD-L1 expression was positive in 90 cases, and the positive rate was 63.8％ (90/141) at a TC1 or IC1 threshold. When a TC3 or IC3 threshold was applied, PD-L1 expression was positive in 17 cases, and the positive rate was 12.1％ (17/141). In the TC1 or IC1 threshold group, PD-L1 expressions were different in patients with different sex, nerve invasion and pleural invasion, and the differences were statistically significant (all P < 0.05). While in the TC3 or IC3 threshold group, PD-L1 expressions were different in patients with different cell differentiation, clinical stage, lymphocyte infiltration, vascular invasion and nerve invasion, and the differences were statistically significant (all P < 0.05). In both TC1 or IC1 threshold group and TC3 or IC3 threshold group, PD-L1 expression was associated with nerve invasion (both P < 0.05). Conclusions PD-L1 expression is associated with nerve invasion. PD-L1 inhibitors expect to be used as a potential treatment strategy for recurrent and progressive lung adenocarcinoma patients with high level expression of PD-L1.

HER2 status in gastric adenocarcinoma of Chinese: a multicenter study of 40 842 patients / 中华病理学杂志

Objective@#To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. @*Methods@#HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. @*Results@#Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . @*Conclusions@#HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Visceral parasitic migration of liver: a clinicopathologic analysis of seven cases / 中华病理学杂志

Objective@#To investigate the clinical, radiological and pathological features of visceral parasitic migration of the liver.@*Methods@#Seven cases of visceral parasitic migration of liver were identified at the Affiliated Drum Tower Hospital of Medical School of Nanjing University from January 2008 to July 2017. Clinical data, enhanced CT image and pathological features were analyzed, combining with literature review.@*Results@#There were 5 male and 2 female patients. Five patients presented with abdominal pain or discomfort as the first symptom. Two patients were admitted to the hospital for physical examination with liver nodule. Blood eosinophils were mildly to moderately increased in 4 cases. Enhanced CT showed the liver irregular beaded nodules that showed no significant enhancement of arterial phase. Mild enhancement of round lesions (ring lesion) was seen in a few cases before surgery. By histopathology, the lesions showed central geographic necrosis, surrounded by epithelioid granuloma and inflammatory cell bands. A large number of eosinophils and scattered multinucleated giant cells were found, especially at the peripheral of the lesion. Charcot-Leyden crystals were present in all case and parasitic migrans was found in one case.@*Conclusions@#Visceral parasitic migration of liver is a rare liver disease and is easily misdiagnosed as other benign or malignant liver tumors. Combining clinical data, enhanced CT images and pathological examination can improve the preoperative and postoperative diagnosis of the disease.

Clinical, endoscopic and pathological features of gastrointestinal and mesenteric reactive nodular fibrous pseudotumor / 中华消化内镜杂志

Objective To study the clinical, endoscopic and pathological features of gastrointestinal and mesenteric reactive nodular fibrous pseudotumor (RNFPT). Methods A retrospective analysis was conducted on data of 24 RNFPT patients in Nanjing Drum Tower Hospital admitted from October 2008 to June 2016. The clinical, endoscopic, pathological and immunohistochemical characteristics were analyzed. Results Among the 24 patients, 16 complained about discomfort in the upper abdomen and 10 had a history of surgery or trauma. Twenty-one had isolated masses and 3 had multiple masses, with diameter of 0. 5-4. 0 cm. Endoscopically, the tumors were mainly hard submucosal masses with broad base, and smooth surface with no mucosal bridge. Seventeen patients underwent endoscopic ultrasonography, which showed low echoes in lesions and nonuniform echoes partly. Among them, 13 lesions derived from muscularis, 4 others from submucosa. Microscopically, the tumors had clear boundary with no envelope, and most areas showed disorderly arranged spindle cells and extensively collagenous degenerated mesenchyma. The spindle cells had shuttle fibroblast-like morphology and elongated nucleus with no visible necrosis or mitosis. Inflammatory cells scattered between the tumor cells, and lymphoid follicles and calcium deposition could be seen in local areas. Immunohistochemically, SMA was focally positive in 7 cases and only 4 cases expressed CD117 scattered. Desmin, Dog-1, CD34, ALK-1 and S-100 were all negative, and Ki-67 proliferation index was lower than 1％. Conclusion RNFPT has diverse clinical manifestations, with a good prognosis and unlikely recurrences, and should be distinguished from spindle cell tumors.

Comparative study of three different decalcifying solutions in bone metastasis specimens with breast cancer / 中华病理学杂志

Objective@#To investigate the optimal strategy for immunohistochemical (IHC) staining in bone metastasis specimens from breast cancer.@*Methods@#Twenty-eight bone metastases specimens from breast cancers were divided into three groups and subjected to different decalcifying agents (group A-10% nitrate, group B-EDTA decalcification, and group C-imported decalcifying solution RapidCal). The effects of those on HE and IHC staining for Ki-67, ER, PR, GATA3, RANK, RANKL, HER2 and HER2 FISH results were assessed.@*Results@#There were no significant differences among three groups in HE morphology and IHC staining. Antigen content in the RapidCal group were all intact; the EDTA group showed a similar staining rate, which was better than the nitrate group (P<0.05). Nitrate group showed marked reduction in nuclear Ki-67 staining, but the loss of cytoplasmic antigens (RANK, RANKL) was less than cell membrane antigen (HER2). For FISH, the RapidCal group and EDTA group showed same results, concordant with IHC staining results. The expression of HER2 protein in the nitric acid group was significantly decreased and chromosome 17 labelling was lost (P<0.05).@*Conclusions@#RapidCal treated bone metastases specimens from breast cancer show excellent sample quality in morphological, IHC and FISH results compared with traditional decalcifying agents. Owing to the longer time of EDTA decalcification, the new decalcifying agent RapidCal plays an important role in quality control and clinical application.

Clinicopathologic characteristics of head and neck carcinoma showing thymus-like element / 中华病理学杂志

Objective@#To investigate clinicopathological features of carcinoma showing thymus-like elements (CASTLE) in the head and neck regions.@*Methods@#Clinicopathological data of 7 patients with CASTLE in the head and neck regions were retrospectively reviewed.Immunohistochemical staining and in situ hybridization for EBER were performed. BRAFV600E mutation was examined by ARMS method in 6 cases.@*Results@#There were 5 females and 2 males with age between 49 and 78 years (average of 65.6 years). All tumors were solitary nodular lesions with an infiltrative border, including 6 intrathyroid tumors and 1 extrathyroid tumor in the laryngeal pharynx.The tumors were 1.7-4.1 cm in diameter (average of 3.0 cm). Four cases demonstrated lymph node metastasis.All patients were alive without metastasis during follow-up, except one consultation case (with FNA sample) developed recurrence at the primary site. The cases showed different immunoreaction to CD5, diffuse immunoreaction with p63, CK5/6 and CD117, but negative staining for TTF1, TG and calcitonin. One case showed positive immunoreaction with Synin less than 30% tumor cells. The Ki-67 labeling index was between 3% and 90%. No BRAFV600E mutation and EB virus infection were detected.@*Conclusions@#Extrathyroid CASTLE involving laryngeal pharynx shows the similar morphological and immunohistochemical features with intrathyroid CASTLE.Immunohistochemical markers of CD5 and CD117 are helpful in the diagnosis. Ki-67 labeling index can be high in CASTLE, especially in lymphoepithelioma type. CD5-negative CASTLE may have neuroendocrine differentiation. BRAFV600E mutation and EB virus may not be involved in the carcinogenesis of CASTLE.

Primary renal neuroendocrine tumors:report of five cases and review of the literature / 中华泌尿外科杂志

Objective To analyze the features of diagnosis, treatment and prognosis of primary renal neuroendocrine tumors, and to improve the understanding of primary renal neuroendocrine tumors. Methods From January 2008 to June 2015, 5 cases of primary renal neuroendocrine tumors were hospitalized and their data was analyzed retrospectively, with 1 male 4 females, aged 40-73 years with the middle age of 48 years.Tumors were all located in the left kidney, whose diameters arranged from 4 to 9 cm, with an average of 6.5cm.One case presented with hematuria, one case was identified because of abdominal pain, and the other three cases were identified via physical examination.Four cases underwent a renal contrast-enhanced ultrasound, which indicated a medium-hypoechoic mass in three cases and a hyperechoic mass in one case.All five cases underwent CT scan, presenting irregularly shape and density. Calcification was found in three cases on plain scanning.Significantly heterogeneous enhancement was found in three cases and moderate heterogeneous enhancement was found in one case on enhanced scanning. Results All five cases underwent operations, with two cases undergoing radical nephrectomy and three cases undergoing partial nephrectomy.Pathological examination showed three cases of tumor cells arranged in a nest slug or ribbon-like infiltrative growth, with no or rare mitosis and no necrosis, which is consistent with renal carcinoids.Three out of 4 renal hilar lymph nodes containing tumor cells were identified in one case. The tumor cells in another case exhibited a ribbon-like arrangement, with some round nuclei, no significant atypia, and rare mitosis, which is consistent with renal atypical carcinoid.Two out of two renal hilar lymph nodes containing tumor cells were identified in this case. The tumor tissue of one case showed morphologically uniform, medium-sized cells arranged in nest slug form with necrosis, a high nuclear cytoplasm ratio, an obvious allotype and frequent mitosis, which is consistent with renal small cell carcinoma.The immunohistochemistry of the five cases indicated synaptophysin( Syn) and chromogranin A ( CgA) positive in varying degree.One case of renal carcinoid relapsed approximately 78 months after partial nephrectomy, following with radical surgery.The other two cases were followed up for 8 or 27 months and no recurrence or metastasis was detected.One case of renal atypical carcinoid was followed up for 4 months after radical nephrectomy and no recurrence or metastasis was detected.One case of renal small cell carcinoma died of multiple organ failure 11 months after radical nephrectomy plus hepatic metastatic carcinoma radio-frequency ablation approximately.Conclusions Primary renal neuroendocrine tumors are rare clinically. Renal neuroendocrine tumors may be expressed as carcinoid, atypical carcinoid or small cell carcinoma, and the clinical manifestations, pathological characteristics and prognosis varied.Primary renal carcinoids may be treated by surgery with a nice prognosis.Patients with primary renal small cell carcinoma require comprehensive treatment, and their prognosis is poor.

Analysis on pathology features and prognosis of appendiceal mucinous neoplasm / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the pathological features and prognosis of appendiceal mucinous neoplasms (AMN) based on WHO classification 2010.</p><p><b>METHODS</b>Seventy consecutive cases of AMN were classified into 5 groups according to WHO classification of digestive system tumors in 2010 including mucinous adenomas/cystadenoma (MA), low grade appendiceal mucinous neoplasms (LAMN), low grade pseudomyxoma peritoneum originated from appendix (PMP-L), invasive mucinous adenocarcinomas (MAC) and high grade pseudomyxoma peritoneum originated from appendix (PMP-H). Clinicopathological features, classification, treatment and prognosis of AMN were investigated retrospectively.</p><p><b>RESULTS</b>There were 11 cases of MA with neoplastic epithelium and mucin being defined in lumen and mucosa but without invasive lesions, and no relapse or death was found. In 41 LAMN cases, mucin was found in submucosa, muscularis proparis, or serosa of appendix, no or only scant mucinous epithelium with low grade dysplasia presented in mucinous pools in most cases (39/41). Among 41 LAMN cases, 3 developed relapse or PMP-L, and no death was observed. In 7 PMP-L cases, low grade dysplastic mucinous epithelium in mucinous pools could be found easily in 3 cases and was very scanty in 4 cases, with 1 relapse and 1 death. Eleven invasive carcinomas were found, including 7 MAC cases and 4 PMP-H cases, with local high grade dysplastic epithelium at least. In these invasive lesions, 4 cases recurred and 3 case died (including 2 recurred cases above). MA and LAMN were both non-invasive neoplasms histologically, however, PMP-L, MAC and PMP-H were regarded as adenocarcinomas according to their biological behavior.</p><p><b>CONCLUSION</b>AMN displays a relatively homogeneous group of neoplasms that pursues a predictable clinical course based on their nature, so it is necessary to diagnose and administrative accurately with consistently standards for these neoplastic entities.</p>

HER2 protein testing in gastric cancer: a retrospective analysis of 1 471 cases during two different periods in a single medical center / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the potential factors in influencing the performance of immunohistochemical testing for HER2 protein in gastric cancers.</p><p><b>METHODS</b>The HER2 protein expression status of 1 471 surgically resected archival gastric cancer cases in Drum Tower Hospital collected during two different periods was retrospectively analyzed. The materials included 957 cases tested during the period from 2007 to 2009 (group 1) and 514 cases from 2012 to 2013 (group 2). The test procedures and results observed during these two periods were compared.</p><p><b>RESULTS</b>The percentages of score 3 HER2 protein expression (14.4%, 74/514 versus 9.5%, 91/957) and score 2 or score 3 HER2 protein expression (27.2%, 140/514 versus 21.7%, 208/957) were both higher in group 2 than in group 1 (P < 0.05). In group 1, the cancer tissue was fixed in 10% formalin, stained manually with HER2 antibody A0485 (Dako) and assessed by different pathologists.In group 2, the tissue was fixed in 10% neutral buffered formalin (pH 7.2), stained using automated immunostaining system (Roche Benchmark XT) with HER2 antibody 4B5 (Ventana) and assessed by a specialized team of pathologists.</p><p><b>CONCLUSION</b>The results of HER2 immunostaining in gastric cancer are influenced by a number of factors including type of fixative, clone number of primary antibody, staining methods and experience of pathologists.</p>

Clinical and imaging features of mass forming chronic pancreatitis / 中华胰腺病杂志

Objectives To investigate the clinical and imaging features discriminating mass forming chronic pancreatitis (CP) from pancreatic carcinoma. Methods The clinical, radiologic, laboratory and pathologic profiles of eleven patients with mass forming CP were reviewed retrospectively. Results The patients with mass forming CP were predominantly older, male, and presented with obstructive jaundice or abdominal symptoms. Serum level of CA19-9 was slightly elevated, generally below 100 U/ml, which was lower than that of pancreatic carcinoma. The diagnostic accuracy of B-ultrasound for mass forming CP was only 18.2% and it could only be the screening method; the diagnostic accuracy of CT was 45.5%, and the main CT features included dilation of main pancreatic duct and the branches, as well as pancreatic pseudocysts or calcification. The findings of MRCP and EUS were irregular dilation of main pancreatic duct and common bile duct, which were similar to pancreatic carcinoma. ERCP could provide imaging characteristics of biliary and pancreatic duct, and the nature of obstruction, the stricture and dilation of biliary and pancreatic duct. When combined with CT scan, ERCP was useful for differentiation from pancreatic head cancer. According to histopathology, a few mass forming CP was autoimmune pancreatitis. Conclusions Mass forming CP is associated with clinical and radiologic features that are similar to those of pancreatic carcinoma. It is necessary to carefully evaluating clinical and imaging findings, laboratory findings and histopathological examinations.

Expression of EZH2 mRNA and protein in human prostate carcinoma and its relationship with cell proliferation / 临床与实验病理学杂志

Purpose To investigate the expression of EZH2 mRNA and protein, and its relationship with tumor cell proliferation in human prostate carcinoma (PCa).Methods A tissue microarray was constructed, which contained 68 dots of formalin-fixed,paraffin-embedded tissue samples, including 48 cases of human PCa.Immunohistochemical markers, including EZH2 and Ki-67,were used on the tissue microarray sections by the immunohistochemical staining method.In situ hybridization (ISH) using an EZH2 oligonucleotide probe was also performed on the tissue microarray sections.Additional 15 cases of benign prostate hyperplasia (BPH) and 12 cases of high grade prostate intraepithelial neoplasia (HGPIN) were used as controls.Results The positive rates of EZH2 protein and mRNA expression were 87.50% and 81.25% in the PCa, 16.67% and 16.67% in the HGPIN,13.33% and 6.67% in the BPH,respectively. There were statistical difference between PCa, HGPIN and BPH, respectively (P0.05).The expression of EZH2 protein was related to Gleason score, TNM stage (P0.05). The expression of EZH2 mRNA was related to TNM stage (P0.05).The staining intensity of EZH2 was positively correlated with the Ki-67 indexes (r=0.746,P<0.05).Conclusions Over-expression of EZH2 which is involved in accelerating proliferation may play an important role in the pathogenesis and progression of human prostate carcinoma. As a molecular marker of prostate carcinoma, EZH2 may serve as a new index for estimating the level of malignancy and progression of the prostate cancer.

Preparation and characterization of Mn-Zn ferrite oxygene nanoparticle for tumor thermotherapy / 生物医学工程学杂志

With the sulfate as the materials and NaOH as precipitator, Mn(0.4)Zn(0.6)Fe2O4 nanoparticles were produced, which are proved to be spinel Mn-Zn ferrite analyzed by X-ray diffraction(XRD). Their shapes are approximately global examined by transmission electron microscopy(TEM) and their average diameter is 50 nm measured with image analysis-system. The Curie temperature was measured and in vitro heating test in a alternating magnetic field was carried out. The results show that the Curie temperature is 105. 407 degrees C, While its magnetic fluid could rise to 43 degrees C - 47 degrees C due to different concentration in a alternating magnetic field. The result provide theoretical and practical evidence to select an appropriate material and concentration for tumor

Preparation and characterization of magnetic nano-particles with radiofrequency-induced hyperthermia for cancer treatment / 生物医学工程学杂志

Mn0.5Zn0.5Fe2O4 nano-particles were prepared by the chemical co-precipitation, their characteristics were observed with transmission electron microscope (TEM), X-ray diffractometer (XRD) and thermal analysis system, and etc. The temperature changes of the nano-particles of Mn0.5Zn0.5Fe2O4 and its magnetic fluid explored in radiofrequency(RF,200 KHz, 4 KW) were measured. The proliferation ratio of L929 cells cultured in soak of Mn0.5Zn0.5Fe2O4 nano-particles were observed. The experiment indicates that the magnetic particles were about 40 nm diameter in average, round, had strong magnetism, and were proved to be consistent with the standard data of chart of XRD. Its magnetic fluid exposed to RF could be heated up to temperature range from 40 degrees C to 51 degrees C due to the amount of the magnetic nano-particles and intensity of the alternating magnetic field. Magnetic nano-particles were found to have no obvious cytotoxicity to L929 cells.

Expression of vascular endothelial growth factor in small cell carcinoma of uterus cervix and its clinical significance / 医学研究生学报

Objective: To study the expression of vascular endothelial growth factor(VEGF) in small cell carcinoma of cervis(SCCC) and its relationship with the clinical and pathological features,so as to predict the metastasis of SCCC,to evaluate the prognosis and to manage a proper treatment. Methods: EnVision two step immunohistochemical method was used to observe the expession of VEGF in the samples of small cell carcinoma of cervis. Results: Four samples were obtained from surgical specimens of the patients with SCCC in our hospital.In all the samples,the expression of VEGF was positive. Conclusion: VEGF is closely related with the oncogenesis and development of SCCC.In the earlier period of SCCC,the lymph node involvement and vascular invasion are common.The aggressive progression of SCCC must have something to do with the highly expression of VEGF.The expression of VEGF can be used as an index in selecting treatment and predicting prognosis of SCCC.

Therapeutic effects of nano-magnetoliposomes containing As_2O_3 combined with magnetic fluid hyperthermia on xenograft cervical carcinoma / 中华物理医学与康复杂志

Objective To explore the inhibition effects and mechanics of nano-magnetoliposomes containing As_2O_3 (NMLA) combined with magnetic fluid hyperthermia on xenograft cervical carcinoma in nude mice. Methods After establishment of xenograft cervical carcinoma models in nude mice, nano-liposomes containing As_2O (NLA group), nano-magnetoliposomes (NML group) and NMLA (NMLA group) were injected into the xnograft cervical carcinoma, respectively, and all nude mice were exposed to AMF for three times. The inhibitive ratios (IR) of the tumors, apoptosis index (AI), proliferation index (PI) and the expression of Bcl-2 and Bax proteins were measured, as well as the function of liver and kidney. Results IRs in NLA, NML and NMLA groups were 57.06% (P0.05). The obvious necrosis was observed in the tumor tissues in NLA, NML and NMLA groups, but not in the peripheral tissues of the tumors and the visceras. Conclusion NMLA, without toxicity of liver and kidney, might be a desirable composite carrier of targeted treatment with chemotherapy and thermotherapy simultaneously.

Mechanism of SIRT1 acting on tumor formation / 医学研究生学报

SIRT1 is an NAD+-dependent histone deacetylase,involved in many physiological processes,such as cell aging,apoptosis and differentiation.Recent studies have shown that SIRT1 plays a significant role in tumor formation and progression.It deacetylates a wide range of histone and non-histone substrates and regulates gene expression and protein activity that are associated with neoplastic apoptosis and proliferation.