Library

Notes: Previous studies have shown that oestrogen receptor content in breast cancer was correlated with qualitative and also, more strongly, with quantitative nuclear features in tissue sections. However, even with the better reproducible quantitative microscopical assessments, the variance in the correlation with oestrogen receptor was considerable. This might be due to the implicit problems of oestrogen receptor determination with the biochemical assay. Therefore, receptor content was studied using monoclonal antibodies in 50 consecutive invasive ductal breast cancers. Oestrogen receptor status was compared with qualitative features and with the mean and standard deviation of the nuclear area, morphometrically evaluated on immunostained and adjacent haematoxylin and eosin stained sections. In agreement with earlier observations, nearly all tumours with prominent elastosis were oestrogen receptor positive; but a minority of negative cases also showed elastosis. The correlation between the other qualitative features and receptor status was weak. A significant inverse correlation (P〈0.001) existed between the receptor status and the mean and standard deviation of the nuclear area. Even with the highly reproducible morphometrical analysis, correlation between nuclear oestrogen receptor content and quantitative nuclear features was relatively weak. This might indicate that receptor status and nuclear morphometric features reflect different biological characteristics of breast cancers.

Notes: Summary Background Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level. Objectives In this study, 32 melanocytic lesions were analysed by FISH, aiming at investigating possible telomere differences among various benign and malignant lesions and correlation with telomerase activity (TA) level. Methods FISH was performed on paraffin sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma metastases and nine control samples of normal skin. Telomere mean maximum diameter (Feret max), area and number per nuclear area were calculated by image analysis on fluorescent images elaborated through KS400 and in situ imaging system (ISIS) for FISH analysis programs. Mean TA level was also calculated in all lesions and correlated with telomere parameters. Results Telomere number per nuclear area was significantly lower in melanomas and metastases than in benign common and Spitz naevi and in control skin (7·24 ± 3·3; 6·11 ± 3 vs. 14·46 ± 5·6; 16·92 ± 7·8; and 12·59 ± 3·4, respectively; P 〈 0·001). No significant differences were found for the other telomere parameters. In common and Spitz naevi, telomere number was positively correlated with Feret max (P = 0·046 and P 〈 0·0001, respectively). TA was significantly higher in melanomas and metastases than in the other groups (70·18 ± 25·2; 105·07 ± 30 vs. 2·16 ± 2·4; 2·99 ± 2·1; 2 ± 1·2, respectively; P≤0·001) and it was inversely correlated with telomere number per nuclear area in melanomas (P = 0·0041). No other significant correlations were found. Conclusions Encouraging results have been obtained from quantitative telomere evaluation in the diagnosis of melanocytic lesions, although an analysis of a larger number of cases would be necessary to provide more reliable data. An extreme shortening of some telomeres probably results in the decrease of telomeric signals and the lower mean number of detectable telomeres in melanomas and metastases. In melanomas, telomere number per nuclear area is also inversely correlated with TA levels. Quantitative FISH of melanocytic lesions could give more specific information at the cellular level in telomere and telomerase fields of investigation.