Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

<p>Abstract</p> <p>Background</p> <p>MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs.</p> <p>Methods</p> <p>From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. <it>KRAS2</it>, the mutation cluster region (MCR) of <it>APC, p53</it>, and <it>SMAD4 </it>were analyzed for somatic mutations.</p> <p>Results</p> <p>MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic <it>APC </it>MCR mutations occurred in 14% (5/36) while 64% (23/36) had <it>KRAS2 </it>mutations (22/23 c.34G>T). G>T tranversions were found in <it>p53 </it>and <it>SMAD4</it>, although the relative frequency compared to other mutations was low.</p> <p>Conclusion</p> <p>MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in <it>APC </it>and <it>KRAS2 </it>(mutated in early tumour development) but not in <it>P53 </it>and <it>SMAD4 </it>(implicated in tumour progression) might indicate a predominant MUTYH effect in <it>early </it>carcinogenesis.</p

Nuclear Localization of CXCR4 Determines Prognosis for Colorectal Cancer Patients

Chemokines and their receptors are implicated in formation of colorectal cancer metastases. Especially CXCR4 is an important factor, determining migration, invasiveness, metastasis and proliferation of colorectal cancer cells. Object of this study was to determine expression of CXCR4 in tumor tissue of colorectal cancer patients and associate CXCR4 expression levels to clinicopathological parameters. Levels of CXCR4 expression of a random cohort of patients, who underwent primary curative resection of a colorectal carcinoma, were retrospectively determined by quantitative real-time RT-PCR and semi-quantitative analyses of immunohistochemical stained paraffin sections. Expression levels were associated to clinicopathological parameters. Using RT-PCR we found that a high expression of CXCR4 in the primary tumor was an independent prognostic factor for a poor disease free survival (p = 0.03, HR: 2.0, CI = 1.1–3.7). Immunohistochemical staining showed that nuclear distribution of CXCR4 in the tumor cells was inversely associated with disease free and overall survival (p = 0.04, HR: 2.6, CI = 1.0–6.2), while expression in the cytoplasm was not associated with prognosis. In conclusion, our study showed that a high expression of nuclear localized CXCR4 in tumor cells is an independent predictor for poor survival for colorectal cancer patients

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment