Kvantitativna mikromorfološka studija lobularnih karcinoma dojke različite biološke agresivnosti

Abstract

This study analyzed lobular breast cancers of 334 female patients, and their micro-morphological, immunohistochemical and quantitative characteristics. The results of breast cancer tissue analysis were compared with patient`s age, tumor dimensions, tumor grade, multicentrical/multifocal tumor growth, and presence/absence of axillary lymph node metastasis. Scientific literature offers more different classification systems of lobular breast cancers, followed by controversy about multifocality/multicentricity, as well as billaterality of these cancers. The most usual types of analyzed lobular breast cancer were: classical 244 (73.1%), and pleomorphic type (15.9%), however none was significantly correlated with multifocal growth or presence of metastases in axillary lymph nodes. Nuclear morphometry showed that invasive lobular breast cancers (ILC), with a larger values of average nuclear area, more often are followed by multifocal tumor growth, or presence of metastases in lymph nodes. The ILC larger than 2 cm, frequently gives metastases in axillary lymph nodes, as well as the absence of immunohistochemically verified estrogene receptors was significantly correlated with metastatic potential of ILCs. A large number of classical type of lobular breast cancers associated with positive ER and PR, higher Ki-67 labeling index, and with lower values of average nuclear area, showed clear difference about mentioned parameters toward pleomorphic type. However, their common histological origin was indirectly demonstrated with absence of statistically significant difference between them about presence of metastases in axillary lymph nodes, multifocal/multicentrical growth ILCs, and about absence of their association with genetic lesions, namely, HER-2 oncoprotein, BRCA1, p53, and E-cadherin. High proliferative activity of breast cancer cells was significantly correlated with overexpression of tumor-supressor p53. All ILC-s with desmoplastic stromal reaction showed overexpression of BRCA1. Finally, in order to avoid subjective bias during chromogene color intensity analysis, immunohistochemical expression of ER was quantitatively performed by using calibrated photometric system. Moreover, statistically significant correlation of percentage and average intensity of immunohistochemical ER presence in nuclei of cancer cells with age of patients was observed. Higher average values of immunohistochemical nuclear intensity staining on ER were statistically more significant at pleomorphic type lobular breast carcinoma patients, than at patients with classical type. It is obvious that quantitative micromorphological analysis could be very useful for unbiased differential diagnostics of ILC`s types, and estimation of their biological aggressiveness.