Tumour budding is associated with hypoxia at the advancing front of colorectal cancer.

AIMS: The tumour budding ability to predict cancer progression is felt to be worthy of investigation with regard to its biological properties. This study was aimed at evaluating the role of hypoxia and microvascularization in the morphogenesis of tumour budding in colorectal carcinoma. METHODS AND RESULTS: The immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX in cancer cells and CD105 in carcinoma-induced microvascularization were assessed in 479 colorectal cancers. Furthermore, MET proto-oncogene, receptor tyrosine kinase (MET) gene amplification was searched using fluorescence in-situ hybridization (FISH). Carbonic anhydrase IX and HIF-1α overall scores differed significantly in low- compared to high-grade tumour budding cancers (P < 0.001), both in pT1 and in pT2-4 tumours. Intratumour analysis of budding foci showed a striking absence of carbonic anhydrase IX immunostain in detaching cells with respect to the surrounding microsectors. The mean microvessel density values were significantly higher in the low- compared to the high-grade tumour budding groups (P < 0.001). A similar copy number of MET gene was detected in the two groups. CONCLUSIONS: Our study shows that tumour budding is associated with hypoxia induced by hypovascularization at the advancing front of colorectal cancer and that budding cells express a HIF-1α-mediated hypoxic tumour phenotype. MET gene amplification is not related to tumour budding morphogenesis.

Technical and clinical description of a case of extensive anogenital Paget's disease associated with anal cancer treated by tomotherapy.

In this paper we describe a case of extramammary Paget's disease associated with anal cancer, which was successfully treated by intensity-modulated radiotherapy using tomotherapy with a simultaneous integrated boost and daily image guidance. The main pitfall in this report is the relatively short follow-up (1 year), which means that the evaluated data is promising but not conclusive. Considering the rarity and wide extension of our patient's Paget's disease in the anogenital region, and the lack of literature reports about curative radiotherapy in this particular setting, this case report may be considered the first related to extensive extramammary Paget's disease treated by tomotherapy.

Virtual microscopy for histology quality assurance of screen-detected polyps.

AIM: Histology quality assurance is crucial for screening programmes and can be performed by circulating glass slides, which has certain intrinsic disadvantages. The present study aimed to assess the accuracy of virtual microscopy in terms of reliability and diagnostic reproducibility in colorectal cancer screening programmes. METHODS: 457 consecutive lesions detected in people undergoing colonoscopy were examined histologically in two pathology units, using both traditional optical microscopy and virtual microscopy (6-12 months later). Intra- and inter-observer agreement using the two approaches was determined using κ statistics. RESULTS: Intra- and inter-observer agreements were substantially unmodified by the use of the virtual microscopy approach compared with traditional optical microscopy; moreover, for some histological features critical for patient management in colorectal cancer screening programmes (such as the presence of a villous component within the adenoma), virtual microscopy increased interobserver agreement (κ statistics 0.66 versus 0.52). CONCLUSIONS: This study shows that virtual microscopy can be an effective tool for diagnostic quality assurance in colorectal cancer screening programmes, and its accuracy is equivalent to or higher than that of optical microscopy in the validation of histological criteria (eg, advanced adenoma) crucial for patient management in screening programmes.

Matrix metalloproteinase type 2 expression in malignant adrenocortical tumors: Diagnostic and prognostic significance in a series of 50 adrenocortical carcinomas.

The differential diagnosis of adrenocortical carcinoma from adrenocortical adenoma is based on different pathological parameters, usually incorporated in scoring systems, which unfortunately lack a 100% sensitivity and specificity. Little is known on the molecular mechanisms leading to the malignant phenotype in adrenocortical tumors. Among other molecules, metalloproteinases were demonstrated to be implicated in malignant progression and metastatization of solid tumors, including endocrine ones. Therefore, we aimed to investigate metalloproteinases and their inhibitors expression in a series of 50 adrenocortical carcinomas and 50 control adrenocortical adenomas, diagnosed according to the Weiss histological criteria. Immunohistochemical results were scored by semiquantitative analysis and compared with clinicopathological parameters and outcome. Metalloproteinase type 2 gave the most significant result, being detected in neoplastic cells in 1/50 adrenocortical adenomas (2%) and 37/50 adrenocortical carcinomas (74%) (P < 0.001), with a focal (score 1, <20% of positive cells--two-thirds of cases) or diffuse (score 2, >20% of positive cells--one-third of cases) pattern. In addition, diffuse (score 2) metalloproteinase type 2 protein expression, as compared to focal or negative immunostaining, correlated with shorter survival (P < 0.02) and disease-free interval (P = 0.05). No correlation was found comparing metalloproteinase type 2 expression and any clinicopathological parameter. Our data indicate that metalloproteinase type 2 immunohistochemical localization in tumor cells is significantly restricted to malignant adrenocortical tumors, with high specificity but low sensitivity. In addition, a strong metalloproteinase type 2 expression in adrenocortical carcinoma was for the first time recognized as an unfavorable prognostic factor.