Phenotypic Drift as a Cause for Intratumoral Morphological Heterogeneity of Invasive Ductal Breast Carcinoma Not Otherwise Specified

Abstract

Invasive ductal carcinoma (IDC) not otherwise specified (NOS), the most common type of breast cancer, demonstrates great intratumoral morphological heterogeneity, which encompasses the presence of different types of morphological structures—tubular, trabecular, solid, and alveolar structures and discrete groups of tumor cells, the origins of which remain unclear at present. In this study of 162 IDC NOS patients, we investigated whether the distribution of different types of morphological structures is related to the basic clinicopathological parameters of IDC NOS. Our results showed that in patients with only one type of tumor structure, the presence of any one of the five types was equally probable; however, cases with two types of structures were more likely to contain trabecular structures than the other four types. The development of intratumoral morphological heterogeneity was not associated with menopausal status, tumor size, histological grade, hematogenic metastasis, or recurrence. However, the number of different types of morphological structures was significantly higher in luminal tumors than in triple-negative tumors. An increase in the frequency of lymph node metastasis correlated with the increased number of different types of structures in breast tumors; however, in contrast to premenopausal patients, this association was explained by the presence of alveolar structures in postmenopausal women. In addition, we showed a significant decrease in the numbers of positive lymph nodes in tumors with high numbers of morphological variants. The frequency of lymph node metastases and the number of positive nodes were generally independent features and formed by different mechanisms. Based on the evidence, the term “phenotypic drift” has been designated as the basis for the development of intratumoral morphological heterogeneity of IDC NOS.

Intratumoral Morphological Heterogeneity of Breast Cancer As an Indicator of the Metastatic Potential and Tumor Chemosensitivity

“…2B ). These findings are in general consistent with the data, which were previously obtained in a smaller sample of patients, on the association between alveolar structures and the rate of lymph node metastasis [7, 10, 11], as well as the association between trabecular structures and the risk of lymph node metastasis [12]. …”

Single Tumor Cells With Epithelial-Like Morphology Are Associated With Breast Cancer Metastasis

“…# IR626, clone MIB-1, RTU). Immunohistochemistry was performed as previously described (11). ER and PR immunostaining was scored using ASCO/CAP Recommendations (12).…”

Invasive and drug resistant expression profile of different morphological structures of breast tumors

“…In contrast, increased cell-cell and cell-matrix interactions were suggested to be associated with the development of the multicellular resistance, which is typical for tumor spheroids and clusters of different cultured tumor cell line types [6]. Intratumor morphological heterogeneity was shown to be related to lymph node metastasis and chemotherapy efficiency of invasive carcinoma of no special type (IC NST) [7][8][9] and invasive micropapillary carcinoma (IMPC) of the breast [10,11]. In spite of some studies clarifying the nature of the contribution of morphological heterogeneity to therapy responsiveness and metastasis of breast cancer [7,10,11], the mechanisms of the above-mentioned associations remain to be identified.…”