Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0-17), intermediat

Infiltrating micropapillary carcinoma of the breast: cytologic findings

To examine the cytologic features of infiltrating micropapillary carcinoma (IMPC). METHODS: Using the histopathology files of one of the authors (I.J.B.), we retrospectively identified 20 IMPC cases (pure, 12; partial micropapillary carcinoma differentiation, 8) with corresponding cytology. We evaluated the cases for cellularity, atypia, architecture and background. RESULTS: All cases were diagnostic of malignancy, characterized by atypical cells present predominantly in three-dimensional clusters and single cells, facilitating the diagnosis. The clusters had cell ball and papillarylike arrangements, like the morular growth pattern seen on histopathology. Apocrine cytology was present in 12 cases, focal mucin background in 5 and psamomma bodies in 2. The differential diagnosis includes primary papillary neoplasms of the breast, metastatic ovarian papillary serous carcinoma, apocrine and colloid carcinoma of the breast, and intraductal carcinoma (micropapillary type). CONCLUSION: As in histopathology, the cytologic features of IMPC are unique and should be recognized due to its aggressive behavior

Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0–17), intermediate (18–30), and high (31) to predict chemotherapy benefit. Our goal was to determine the association between histomorphology, immunohistochemistry, and RR. We retrospectively identified 536 patients with ER+ and LN− breast cancers that underwent Oncotype testing from 2006 to 2013. Tumor size ranged from 0.2 cm to 6.5 cm (mean = 1.3 cm) and was uniform in all 3 categories. The carcinomas were as follows: ductal = 63.2%, lobular = 11.1%, and mixed = 35.7%. The RR correlated with the Nottingham grade. Increasing RR was inversely related to PR positivity but directly to Her2 positivity. Of the morphologic parameters, a tubular(lobular) morphology correlated only with low-intermediate scores and anaplastic type with intermediate-high scores. Other morphologies like micropapillary and mucinous were uniformly distributed in each category. Carcinomas with comedo intraductal carcinoma were more likely associated with high RR. Forty-four patients with either isolated tumor cells or micrometastases were evenly distributed amongst the 3 RR. While there was only 1 ER discrepancy between our immunohistochemistry (3+ 80%) and Oncotype, up to 8% of PR+ cases (mean = 15%, median = 5%) and 2% of HER2+ cases were undervalued by Oncotype

N-cadherin Expression in Breast Cancer: Correlation with an Aggressive Histologic Variant – Invasive Micropapillary Carcinoma

Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n=114) for N- and E-cadherin. These specimens compared invasive duct carcinomas (IDCs) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast (MPAP), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-MPAP and MPAP IDCs, and between the invasive and ductal carcinoma in situ (DCIS) of each IDC using statistical analysis. We found that N-cadherin was expressed in 76% of MPAP and 52% of non-MPAP carcinomas, and E-cadherin in 57% of MPAP and 36% of non-MPAP tumors. More MPAP (25%) compared to non-MPAP (5%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with MPAP tumors (p=0.033) compared to E-cad (p=0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the IDC relative to intraductal components, and this effect was more dramatic in the MPAP carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the MPAP group (p=0.005), whereas such changes were not significant in the non-MPAP group (p=0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression

Histologic grading of breast carcinoma: A multi-institution study of interobserver variation using virtual microscopy

Breast carcinoma grading is an important prognostic feature recently incorporated into the AJCC Cancer Staging Manual. There is increased interest in applying virtual microscopy (VM) using digital whole slide imaging (WSI) more broadly. Little is known regarding concordance in grading using VM and how such variability might affect AJCC prognostic staging (PS). We evaluated interobserver variability amongst a multi-institutional group of breast pathologists using digital WSI and how discrepancies in grading would affect PS. A digitally scanned slide from 143 invasive carcinomas was independently reviewed by 6 pathologists and assigned grades based on established criteria for tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). Statistical analysis was performed. Interobserver agreement for grade was moderate (κ = 0.497). Agreement was fair (κ = 0.375), moderate (κ = 0.491), and good (κ = 0.705) for grades 2, 3, and 1, respectively. Observer pair concordance ranged from fair to good (κ = 0.354-0.684) Perfect agreement was observed in 43 cases (30%). Interobserver agreement for the individual components was best for TF (κ = 0.503) and worst for MC (κ = 0.281). Seventeen of 86 (19.8%) discrepant cases would have resulted in changes in PS and discrepancies most frequently resulted in a PS change from IA to IB (n = 9). For two of these nine cases, Oncotype DX results would have led to a PS of 1A regardless of grade. Using VM, a multi-institutional cohort of pathologists showed moderate concordance for breast cancer grading, similar to studies using light microscopy. Agreement was the best at the extremes of grade and for evaluation of TF. Whether the higher variability noted for MC is a consequence of VM grading warrants further investigation. Discordance in grading infrequently leads to clinically meaningful changes in the prognostic stage

N-cadherin Expression in Breast Cancer: Correlation with an Aggressive Histologic Variant – Invasive Micropapillary Carcinoma

Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n=114) for N- and E-cadherin. These specimens compared invasive duct carcinomas (IDCs) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast (MPAP), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-MPAP and MPAP IDCs, and between the invasive and ductal carcinoma in situ (DCIS) of each IDC using statistical analysis. We found that N-cadherin was expressed in 76% of MPAP and 52% of non-MPAP carcinomas, and E-cadherin in 57% of MPAP and 36% of non-MPAP tumors. More MPAP (25%) compared to non-MPAP (5%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with MPAP tumors (p=0.033) compared to E-cad (p=0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the IDC relative to intraductal components, and this effect was more dramatic in the MPAP carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the MPAP group (p=0.005), whereas such changes were not significant in the non-MPAP group (p=0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression