Prognostic significance of tumour budding, tumour–stroma ratio and desmoplastic stromal reaction in gall bladder carcinoma

Aims and methodsThe prognostic role of tumour budding (TBd) and its interaction with the stromal microenvironment has gained a lot of attention recently, but remains unexplored in gall bladder cancer (GBC). We aimed to study the interrelationship of TBd by International Tumour Budding Consensus Conference scoring system, tumour–stroma ratio (TSR) and desmoplastic stromal reaction (DSR) with the conventional clinicopathological prognostic factors, mortality and overall survival (OS) in 96 patients of operated GBC.ResultsHigher age, high TNM stage, lymphovascular and perineural invasion, positive resection margins, higher TBd score, low TSR and immature DSR were significantly associated with worse OS. However, on multivariate analysis, only metastases, positive resection margins and TSR <50% proved to be independent prognostic factors. The TBd score of stroma-rich tumour group (6.40±4.69) was significantly higher than that of stroma-poor group (2.77±3.79, p≤0.001). The TBd score of immature and intermediate DSR groups was significantly higher than that of mature group (p≤0.001 and p=0.002, respectively). There was a strong interobserver agreement for TBd score, TSR and type of DSR (Cohen’s Kappa=0.726 to 0.864, p≤0.001). Stroma-rich tumours were significantly associated with immature DSR and fibrotic DSR with high TSR (p≤0.001).ConclusionA high TBd, low TSR and immature DSR were significantly associated with several high-risk clinicopathological parameters and poor OS in GBC. These novel, simple, reproducible and cost-effective parameters may be included in the routine reporting checklist for GBC as additional prognostic parameters that can substratify the high-risk patients.

Increased Expression of Type-I Collagen in Malignant Colorectal Lesion and Positive Correlations with Clinical Factors

Objective Type-I collagen (Col-I) is one of the main macromolecules of the extracellular matrix, and it is involved in the desmoplastic stromal reaction, an indicator of worse prognosis in cases of colorectal cancer (CRC). The purpose of the present study was to investigate Col-I expression in cases of CRC and adenoma and to correlate with the clinical data and the data regarding the lifestyle of the patients. Methods A retrospective study including 22 patients with adenoma and 15 with CRC treated at a coloproctology service. The clinical and lifestyle data were obtained through medical records, and Col-I expression was investigated by immunohistochemistry. Results Women represented most cases of adenoma (63.64%), whereas CRC was found mainly in men (73.33%) (p = 0.0448). Immunoexpression of Col-I showed a basement membrane thickening in areas of lining of epithelium and around the glands in both lesions. The cases of CRC had a quite evident fibrosis process in the stroma. The quantitative analysis demonstrated a higher protein expression in CRCs compared to adenomas (p = 0.0109), as well as in female patients (p = 0.0214), patients aged ≥ 50 years (p = 0.0400), and in those with a positive family history of colorectal disease (p = 0.0292). These results suggested a remodeling of the microenvironment of the tumor in CRC carcinogenesis. Importantly, the clinicopathologic positive correlations showed a plausible link between the patient's profile and the immunohistochemical findings, which indicate a possible form of patient stratification. Conclusion The immunohistochemical analysis encourages the performance of more comprehensive studies to ascertain if our results could be a tool for the diagnosis and monitoring of the patients.

Expression of Extracellular Matrix-Related Genes and Their Regulatory microRNAs in Problematic Colorectal Polyps

Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for DCN, EPHA4, FN1, SPON2, and SPP1, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs hsa-miR-200c and hsa-miR-146a significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for hsa-miR-29c. The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future.

Gastric Myeloid Metaplasia: A Case Report and Review of the Literature

We report a case of gastric myeloid metaplasia in an 89- year-old woman with agnogenic myeloid metaplasia. The lesions were fortuitously discovered on upper endoscopy. The antral mucosa was thickened and polypoid, and on histologic examination contained immature granulocytes, megakaryocytes, and a few erythroblasts without desmoplastic stromal reaction. The granulocytes were positive for CD15, CD68, and myeloperoxidase on immunohistochemistry, and the megakaryocytes showed positive reactivity for factor VIII. Gastric myeloid metaplasia is a very rare event, and to our knowledge only 6 cases have been reported in the literature to date. It usually occurs in patients with advanced myeloproliferative syndrome. Gastric myeloid metaplasia often has a pseudotumoral appearance, leading to digestive symptoms. Histologic diagnosis is straightforward when trilinear hematopoietic elements are identified in gastric biopsies. Immunohistochemistry with anti–factor VIII antibody can be useful to confirm the presence of megakaryocytes.