Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis.

Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin (ASPN) and decorin (DCN), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFß in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFß pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFß, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFß. Possible activation of the canonical TGFß pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFß with ASPN in GC and DCN with TGFß in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFß interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients.

Prognostic Utility of Cyclin D1 in Invasive Breast Carcinoma.

Invasive breast carcinoma is the most common cancer among women worldwide. Increase in early detection of breast carcinoma by different diagnostic modalities led to decrease in cancer-related mortality and morbidity. Multiple factors and genes are implicated in breast cancer pathogenesis. Cyclin D1 is an important cell cycle regulatory protein involved in carcinogenesis of various human cancers including breast cancer. Aims of the present study were to evaluate the prognostic importance of cyclin D1 expression in invasive breast carcinoma and its correlation with other prognostic and predictive factors. Patients undergoing mastectomy for breast carcinoma were selected from January 2016 to June 2017 in a tertiary care hospital. Clinical history including demographic parameters was collected in the study pro forma. Immunohistochemical staining for ER, PgR, HER2 and cyclin D1 was performed on all cases. The clinicopathological parameters like age, tumour size, histologic grade, histological type, lymphovascular invasion, axillary lymph node metastasis, ER, PgR and HER2 status were compared and correlated with cyclin D1 expression. Cyclin D1 expression found in 60% cases of breast carcinoma. Expression of cyclin D1 showed a highly significant correlation with histological grade (p = 0.000). Cyclin D1 expression showed significant correlation (p = 0.000) with molecular subtypes. There was also significant correlation between cyclin D1 expression and ER (p = 0.000) and PgR (p = 0.010) status. This study revealed significant cyclin D1 expression in low grade, well-differentiated breast cancer. Therefore, we found cyclin D1 as a favourable prognostic marker in breast carcinoma.

Expression of CDX-2 and Ki-67 in different grades of colorectal adenocarcinomas.

BACKGROUND: CDX2 is a caudal homeobox gene essential for intestinal differentiation and is specifically expressed in colorectal adenocarcinomas. Its role in colorectal carcinogenesis is not fully elucidated. AIMS AND OBJECTIVES: To study the expression pattern of CDX2 and Ki-67 in different grades of colorectal adenocarcinomas and to observe the relationship of their staining patterns in various tumor stages and to look for correlation if any, between Ki-67 labeling index (Ki-67 LI) and CDX2 expression. MATERIALS AND METHODS: A total of 74 cases were enrolled. Detailed clinical profile, peroperative findings, histological grading and staging were noted. Immunohistochemistry for CDX2 and Ki-67 was done, and Ki-67 LI was calculated. CDX2 staining was graded semi-quantitatively, and statistical analysis was done. RESULT: Age of presentation ranged from 20 to 75 years, and the male:female ratio was 1.83:1. There were 8, 47 and 13 cases of well, moderate and poorly differentiated adenocarcinomas, respectively. The mean Ki-67 LI of well, moderate and poorly differentiated adenocarcinomas were 14.25, 31.34 and 43.08 respectively, and their difference was statistically significant, correlation was also noted with stage. CDX2 expression appeared to be stronger in poorly differentiated cases, but there was no significant difference in its expression in the different grades and stages. There was no correlation between Ki-67 LI and CDX2 immunostaining pattern. The lymph node metastasis showed CDX2 positivity in all the cases. CONCLUSION: Expression of CDX2 does not significantly change with the grade of colorectal adenocarcinomas. However, it is an important diagnostic marker in metastatic colonic lesions. The Ki-67 LI, on the other hand, showed a strong correlation with histopathological grades.

Inflammatory Myofibroblastic Tumor Arising in the Pancreatic Head: a Rare Case Report.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplastic lesion with tendency toward local aggressive behavior and recurrence. It is primarily a visceral and soft tissue tumor; however, involvement of pancreas is extremely unusual. A localization in the pancreas needs differentiation from other tumors and chronic pancreatitis. We report a case of inflammatory myofibroblastic tumor arising in pancreatic head in a 32-year-old female who underwent Whipple's procedure.

Comparative evaluation of six cytological grading systems in breast carcinoma.

BACKGROUND: Cytological grading is a useful tool for selection of therapy and prognosis in breast carcinoma. Despite having many cytological grading systems, there is still no agreement among pathologists to accept one of them as a gold standard. AIM: This study was undertaken to evaluate six such three-tier cytological grading systems to determine which system corresponds best to histological grading done by Nottingham modification of Scarff Bloom Richardson (SBR)'s method. MATERIALS AND METHODS: In a double-blind study, preoperative cytological grades obtained by six systems on fine-needle aspiration cytology (FNAC) smears were compared by testing concordance, association and correlation with histological grade derived postoperatively by the SBR's method in 57 patients of breast carcinoma. Bivariate correlation studies and multiple linear regressions were done to assess the significance of the different cytological parameters to predict final cytological grades. RESULTS: Robinson's system demonstrated the best correlation (ρ = 0.799; P = 0.000 and τ = 0.765; P = 0.000), maximum percent agreement (77.19%) and a substantial kappa value of agreement (κ = 0.62) with the SBR's grading system. All the six cytological grading systems correlated with histological grading strongly and positively. In multiple regression analysis, all of the cytological parameters of Robinson's system except cell size and nucleoli had significance in predicting the final cytological grade. CONCLUSIONS: Robinson's grading system is simple, more objective and reproducible, and demonstrated the best concordance with histological grading. So, Robinson's system should be used routinely for breast carcinoma aspirates.

Mucin histochemistry of stomach in metaplasia and adenocarcinoma: An observation.

BACKGROUND: There is a variable pattern of occurrence of gastric carcinomas world-wide, partially reflecting the frequency of various changes of gastric mucosa from, which such neoplasm occur. Many cases of gastric carcinoma originate in the background of chronic gastritis caused by Helicobacter pylori. Subsequent intestinal metaplasia (IM) can be morphologically classified by routine and special histopathological stains. MATERIALS AND METHODS: The present study was conducted over the 2 years at NRSMC & H, Kolkata. Aims of the present study were to search for evidences of H. pylori infection, classification of different metaplastic and/or malignant changes, identification of types of mucin by mucin histochemistry and their interrelationship in gastrectomy and gastric biopsy specimens (total 70). After obtaining clinical history, radiological and endoscopic findings were noted. After macroscopic study of the specimen, hematoxylene and eosin, southgate mucicarmine, periodic acid schiff-alcian blue (PAS-AB) and gomori aldehyde fuchsin (GAF)/AB staining were performed to classify gastric carcinoma and metaplastic changes and to correlate with staining patterns of mucin. RESULTS: The overall male to female ratio was 2.89:1. Age ranged from 22 years to 78 years and the commonest age group of gastric carcinomas being 41-50 years (26 cases, 37.1%). Gastric adenocarcinoma was found in 61 (87.1%) cases (22.9% were of intestinal type and 77.1% of diffuse type) and only IM was found in 9 (12.9%) cases. Overall the rapid urease test was positive in 18 (25.7%) cases majority of which showing either pure IM or IM associated with intestinal type of gastric carcinoma. All diffuse types of gastric carcinoma (47 cases, 77.1%) were showed PAS positive staining (indicating neutral mucin) whereas in 15 (65.2%) cases of IM columnar cells stained with AB (representing acidic mucin). GAF/AB stain revealed Type II IM in 10 (43.5%) cases and Type III IM in 4 (17.4%) cases. CONCLUSION: Routine and special histological staining is particularly useful for histological subtyping of gastric carcinomas and IMs.

Extraovarian granulosa cell tumor.

Extraovarian granulosa cell tumor (GCT) is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15 cm x 16 cm and another mesenteric mass of 8 cm x 5 cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA) were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.