ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines.

Breast cancers that overexpress the ERBB2 tyrosine kinase receptor may be treated with the recombinant humanized monoclonal anti-ERBB2 antibody trastuzumab (herceptin). However, resistance to this targeted therapy is frequent. We have determined the response of 18 breast tumor cell lines to trastuzumab and compared it with the ERBB2 phosphorylation status using antibodies directed against tyrosine residue 1248. We show that sensitivity to trastuzumab is frequently associated with the expression of a phosphorylated ERBB2 protein.

Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.

Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines.

Recurrent chromosome breakpoints in tumour cells may point to cancer genes, but not many have been molecularly characterised. We have used multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) on breast tumour cell lines to identify regions of chromosome break created by inversions, duplications, insertions and translocations on chromosomes 1, 5, 8, 12 and 17. We delineate a total of 136 regions of break, some of them occurring with high frequency. We further describe two examples of dual-colour FISH characterisation of breakpoints, which target the 1p36 and 5p11-12 regions. Both breaks involve genes whose function is unknown to date. The mbanding-FISH strategy constitutes an efficient first step in the search for potential cancer genes.

Ultrasonographically guided fine needle aspiration cytology and core-needle biopsy in the diagnosis of breast tumors.

The present study was designed to assess the performance of fine needle aspiration cytology (FNAC) and core-needle biopsy (CNB) of breast lesions when these procedures are performed under sonographic guidance. The results obtained in 1142 FNAC procedures and 180 CNB procedures were analysed. The study took place in a University Hospital and a private practice clinic. The patients eligible for this study were a series of women, in whom at least one hypoechoic, limited mass was found at breast ultrasonography. Cystic masses were excluded from the study. Each individual mass was investigated using either FNAC or CNB under sonographic guidance. Accuracy characteristics to suspect or diagnose malignant and pre-malignant breast lesions, such as sensitivity and specificity, were calculated. The cytological results were classified into four categories according to standard criteria: benign; atypical and/or suspicious for cancer (hyperplasia with atypia); malignant; and unsatisfactory for diagnosis specimen. Tissue specimens were classified according to the W.H.O. The 1142 lesions submitted to FNAC included 66 invasive carcinomas, 4 intraductal carcinomas, and 4 atypical hyperplasias. FNAC led to 6 false-negative examinations, equally distributed between small (volume < or = 1 cm3), and larger lesions, and 1 false-positive examination. There were 12.9% (147/1142) inadequate smears. Only 3 inadequate samples were obtained in the presence of a discrete pathologic lesion (3/363, or 0.1%). All 3 corresponded to invasive carcinomas. The majority of inadequate samples (144/147, or 98.0%) were obtained in the normal/dystrophic group. Overall, the sensitivity is 92.1%, and the specificity is 84.8%. The 180 lesions submitted to CNB included 31 invasive carcinoma, 5 intraductal carcinomas, and 17 atypical hyperplasias. CNB, in this series, had an accuracy rate of 100%. In conclusion, US guidance increases the accuracy of breast tissue sampling procedures. This is of particular importance as the number of suspicious images to be investigated steadily increases, as the result of mass screening.

[Neo-vagina by sigmoid reconstruction. Apropos of 12 cases of vaginal aplasia]. / Néo-vagin par plastie sigmoïdienne. A propos de 12 observations d'aplasie vaginale.

Sigmoid transplants for reconstruction of an aplastic vagina were performed in 12 patients. The technique of cleavage, through a simple perineal or a double approach, raises two problems. First, the slow spontaneous epithelialization means that the new passage must be lined with a skin graft, which is rarely totally successful and prolongs the hospital stay period. Second, the need to wear a mandrin permanently in order to preserve the anatomical result. Sigmoid transplants provide a good and lasting functional result without too many postoperative problems: when performed in young patients, with healthy colons, the morbidity is not modified when compared with that of cleavage operations.