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Aims: To study the association between morphological changes of the bronchial epithelium and its angiogenic status evaluated by microvessel count (MVC), in order to gain a better understanding of bronchial carcinogenesis. Also, to correlate MVC with epidermal growth factor receptor (EGFR) expression. Methods and results: Eighty-three biopsy specimens were assessed for MVC: four normal bronchial epithelia, 23 hyperplasias, 26 metaplasias, two mild dysplasias, five moderate dysplasias, nine severe dysplasias, three carcinomas in situ, six early invasive squamous cell carcinomas (EIC) and five cases of micropapillomatosis. We observed a statistically significant difference in terms of MVC between EIC and all other subgroups and between micropapillomatosis and all other subgroups. There was also a statistically significant difference between micropapillomatosis and EIC. We did not observe any difference in MVC between normal mucosa, metaplasias, hyperplasias, dysplasias or carcinoma in situ. EGFR expression was higher in severe dysplasia, carcinoma in situ and EIC, whereas it was very low in micropapillomatosis. A statistically significant difference was observed in the expression profile of EGFR vs. MVC. EGFR expression was increased in severe dysplasia, whereas an increase in MVC occurred only in EIC. Conclusion: During bronchial carcinogenesis, except for micropapillomatosis, EGFR expression appears to be a prerequisite for neoangiogenesis in bronchial carcinogenesis. [ABSTRACT FROM AUTHOR]

Meert A-P, Feoli F, Martin B, Verdebout J-M, Mascaux C, Verhest A, Ninane V & Sculier J-P (2004) Histopathology 44, 47–53 Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study : The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy. : The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty-one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high- and low-grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant ( P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 ( P = 0.05 between MiD plus MoD versus SD plus CIS). : Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD. [ABSTRACT FROM AUTHOR]

We retrospectively investigated 17 cases of primary and metastasizing Merkel cell carcinomas (MCC) from 14 patients using chromosomal in-situ hybridization (CISH) to study the occurrence of trisomy 6 in these lesions. Methods and results Histological diagnosis on all tumour samples was obtained on haematoxylin and eosin stained sections. Immunohistochemistry was performed with antibodies against pancytokeratin (CAM 5.2), cytokeratin 20 (CK20), MIC2 antigen (CD99), neuron-specific enolase (NSE), and chromogranin A (chrA). Sections (4 µm) of the paraffin-embedded tumours were analysed with α-satellite centromeric probes for chromosome 6 or 17 using CISH. The signal was amplified by the Tyramide Signal Amplification (TSA) assay. Immunohistochemically, the tumours showed the same general epithelial neuroendocrine pattern: 11/13 expressed cytokeratin 20, and 47% exhibited trisomy 6, with no significant difference between primary and metastatic lesions. Incomplete follow-up data did not allow us to establish a prognostic value of trisomy 6, however, this aberration might be an additional diagnostic tool in distinguishing MCC from other small round blue cell tumours. Conclusions CISH seems to be a promising adjunctive method to diagnose Merkel cell carcinoma. Trisomy 6 should be investigated more closely in these cases, as has been done for chromosomes 1 and 11. Of particular interest would be identification of modifications in proto-oncogene(s) located on chromosome 6. [ABSTRACT FROM AUTHOR]

Incidence of anal cancer is increasing and risk of anal cancer is higher in MSM, especially if they are HIV+. European guidelines for treatment of HIV-infected adults recommend anal cancer screening by digital rectal exam±Pap test with anuscopy if Pap test is abnormal. A systematic anal cancer screening in HIV+MSM with anal cytology (Pap smears) was established in June 2011 in our reference centre in Brussels. If anal cytology was abnormal, high-resolution anuscopy (HRA) with biopsy was performed. 353 MSM HIV+were screened by anal smears between June 2011 and May 2012. 90% were Caucasians, median age was 44.5 years, 83% were on HAART and 74% had an undetectable viral load, median CD4 was 632/µl and 33% had a nadir CD4<200. Thirty-three (9.3%) were excluded because of poor quality. Cytology was abnormal in 46% of the 320 remaining patients: high-grade squamous intraepithelial lesion (HSIL) 3%, low-grade squamous intraepithelial lesion (LSIL) 24%, atypical squamous cells of undetermined significance (ASC-US) 16%, and atypical squamous cells / cannot rule out a high-grade lesion (ASC-H) 3%. Viral load (VL) was more frequently undetectable (82% vs 64%, p=0.0003) and median duration of HAART was longer (111 vs 61 months, p=0.0145) in patients with normal cytology. 80 HRA with biopsies have been performed. 12.5% were normal, 44% showed anal intraepithelial neoplasia (AIN) 1, 24% AIN 2 and 19% AIN 3. For this analysis, high-grade AIN (2 and 3) were put together (AIN 2+). Among patients with AIN 2+(n=33), cytology had showed 8 (24%) ASC-US, 3 (9%) ASC-H, 19 (57%) LSIL, 3 (9%) HSIL. When patients with normal cytology or normal biopsy and patients with AIN 2+were compared, the only significant risk factor found for AIN 2+was a nadir CD4<100/µl (32% of the patients with AIN 2+vs 14% in patients with normal smear, p=0.0073). Anal precancerous lesions are frequent and at different stages. Among 46% abnormal cytology, 87% had abnormal biopsy including half AIN 2+.Cytology±biopsy is the only way to detect those lesions and should be performed systematically in HIV+MSM. Risk factor for AIN2+was a nadir CD4<100/µl. A normal cytology was associated with an undetectable VL and a longer duration of HAART. Those results provide further argument for early initiation of HAART. [ABSTRACT FROM AUTHOR]