The Quantitative ER Immunohistochemical Analysis in Breast Cancer: Detecting the 3 + 0, 4 + 0, and 5 + 0 Allred Score Cases.

The currently used immunohistochemical approach in determining the estrogen receptor (ER) positivity of breast cancers (BCs) is inherently subjective and additionally limited by its semi-quantitative nature. The application of software in the analysis of digitized slide images may overcome some of these limitations. However, the utilization of such an approach requires that the entire staining procedure is standardized. BACKGROUND AND OBJECTIVES: We aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters that can possibly be used for a diagnostic purpose that is in line with the current semi-quantitative scoring system. MATERIALS AND METHODS: Semi-quantitative analysis of ER-stained tissue sections was performed following the Allred scoring system guidelines. The quantitative analysis was performed in ImageJ software after color deconvolution. The quantitative analysis of 66 cases of invasive lobular BC included: Percent of ER-positive cells, average nuclear coloration intensity, and the quantitative ER score. The percent of ER-positive tumor cells was counted using a standard grid overlay, while optical density (0.0-1.0) was measured within each nucleus at the grid points. RESULTS: A statistical analysis revealed a significant positive correlation (r = 0.886, p < 0.001) between the subjective semi-quantitative and quantitative ER scores, with a large effect size (d = 3.8215). We observed strong statistically significant correlations between individual parameters of the total ER score, percentage of ER-positive nuclei, and color intensity, obtained by the two independent methods. CONCLUSIONS: Additionally, besides excluding subjectivity, the up to now unreported cases of 3 + 0, 4 + 0, and 5 + 0 Allred scores were detected only by the application of the proposed quantitative approach.

Immunohistochemical features of multifocal and multicentric lobular breast carcinoma.

PURPOSE: Patient age, tumor size, axillary lymph node status, expression of estrogen, progesterone and HER2 receptors, as well as the histological grade, are widely accepted prognostic and predictive parameters in breast carcinoma. In invasive lobular carcinoma (ILC), the prognostic factors, such as nodal status and tumor size are believed to be the most valuable ones. The aim of this was set to determine the possible linkage between MFity/MCity of ILC and immunohistochemical predictive (ER, PR, HER2) and prognostic parameters (BRCA1, p53, E-cadherin, Ki-67). MATERIAL/METHODS: Out of 2486 cases diagnosed with BC from south-eastern Serbia, the presence ILC was noted in 334 cases. Immunohistochemical characterization of predictive and prognostic parameters in ILC was done. RESULTS: The occurrence of multifocal (MFC) and multicentric carcinoma (MCC) was observed in 18.9% of ILC. Bilateral (BL) BCs were found to be statistically significantly more frequent in younger women, compared to those with MFC, MCC or nonMFC/MCC/BL. No significant correlation was found between MFC/MCC and the presence of axillary lymph node metastases, and expression of immunohistochemical predictive and prognostic parameters. Based on literature data and the findings from the current work, MFity/MCtiy might represent negative morphologic prognostic parameters in ILC. CONCLUSIONS: In 334 cases analyzed, no statistically significant correlations were observed between MF/MC and the expression of immunohistochemical predictive and prognostic parameters.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

PURPOSE: The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. METHODS: Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. RESULTS: Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. CONCLUSIONS: Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

Evaluation of pathological parameters and morphometric data of desmoplastic lobular breast carcinoma.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most frequent form of breast cancer. While cancer cells are regularly investigated, tumor stroma represents a highly unexplored field. AIMS: The aim of this study is to perform a detailed investigation of clinical, immunohistochemical, and morphometric characteristics of desmoplastic (D) and nondesmoplastic (ND) ILC. MATERIALS AND METHODS: This study included twenty cases of ILC that were divided into two groups designated as D and ND groups. Medical histories and diagnosis data were obtained from the archives of the Center of Pathology, Clinical center Nis (Serbia). Morphometric analysis of hematoxylin and eosin stained slides was performed using ImageJ software, and the obtained data were further statistical processed. RESULTS: Statistical analyses of the data revealed that no significant differences between D and ND groups when patient age, estrogen receptor (ER), and progesterone receptor (PR) expressions and morphometrical parameters (such as the distance between groups of cancer cells and nucleocytoplasmic ratio) were compared. However, D and ND groups statistically, significantly differed in the occurrence of axillary lymph node metastasis, and when the ER and PR data were included, in certain nuclear parameters (cell/nucleus area, perimeter, Feret's diameter, and circularity). CONCLUSIONS: Desmoplastic stroma was observed more frequently in patients without axillary lymph node metastases, whereas the expression of ER and PR had no influence on its development. According to the measured morphometric parameters larger cells/nuclei belonged to ND group.