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.

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.