Remarkably High Frequency of EGFR Expression in Breast Carcinomas with Squamous Differentiation

Abstract

The human epidermal growth factor receptor (EGFR) is reportedly overexpressed in 15-20% of breast carcinomas. EGFR overexpression is associated with reduced survival and is inversely correlated with expression of estrogen receptor (ER). This study assessed EGFR expression in breast carcinomas with squamous differentiation. The immunohistochemical (IHC) expression of EGFR was evaluated in 39 breast carcinomas with squamous differentiation (30 pure squamous, 6 adenosquamous, 3 carcinosarcomas) by use of the pharmDx assay (clone 2-18C9, DakoCytomation). Cases were considered positive if at least 10% of the cells showed 1+ positivity in the squamous component. Squamous differentiation was confirmed with IHC for CK5-6 (clone D5/16B4, DakoCytomation). ER, PR, and HER2 status as well as clinical information regarding treatment and outcome were correlated. As a control, a tissue microarray comprising 280 lymph node positive breast carcinomas was evaluated with the same EGFR assay. The 39 patients ranged in age from 33 to 77 years (mean 52). The tumors measured 1.3-30 cm (mean 4.8). Sentinel or full axillary lymph node dissection was performed in 28 patients. Fourteen patients had positive lymph nodes. At the time of initial diagnosis, 3 patients had distant metastasis. Follow-up was available for 16 patients (mean 45 months). Disease-free survival at 3 years was 70%. Among the 39 tumors 87% (34) were positive for EGFR (p<0.0001). Sixty-nine percent (27 of 39) showed >50% 2+ EGFR staining. EGFR-positive tumor cells (showing squamous morphology) were also found in 1 bone, 1 lung, and 8 of 11 lymph node metastases available for evaluation. All 11 lymph nodes showed squamous differentiation. All but 1 of the EGFR+ tumors examined were ER and PR negative. Six EGFR-positive tumors were HER2 positive. No statistically significant differences in HER2 status, size, lymph node status and disease-free survival were observed between EGFR+ and EGFR- cases, but the number of EGFR-negative tumors was quite small. Nine of 280 (3%) of lymph node-positive invasive carcinomas on the tissue microarray were EGFR+; review of the initial diagnostic slides failed to reveal squamous features in all but 1 of the 9 EGFR+ tumors. Breast carcinomas with squamous differentiation are a distinct subgroup of breast tumors with a very high frequency of EGFR positivity. Breast carcinomas of this type would be ideal candidates for a trial with EGFR inhibitors.

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

“…EGFR is reportedly overexpressed in 15-20% of breast carcinomas, 37 which is in the range found in this series of primary tumours. In brain metastases, however, the incidence was found to be higher ranging to 41%.…”

A Targetable Androgen Receptor–Positive Breast Cancer Subtype Hidden Among the Triple-Negative Cancers

“…Among carcinomas of special types, the squamous and myoepithelial carcinomas are epidermal growth factor receptor (EGFR) positive and could potentially benefit from EGFR-targeted therapy. [10][11][12] About 25% to 75% of TNBCs show androgen receptor (AR) expression; many, but not all, of these tumors are apocrine carcinomas. [13][14][15][16][17] It is this latter group (AR þ TNBCs) that is of special interest in this review for a potential benefit from AR-targeted therapies.…”

Gallbladder Squamous Cell Carcinoma with Chronic Right Upper Quadrant Discomfort

“…This, however, may not be surprising as squamous differentiation in carcinomas of glandular organs often occur as a result of 'metaplastic' change, which often occurs as a part of 'dedifferentiation'. 33,35,36,48 For example, in the breast, squamous differentiation is often a part of sarcomatoid carcinomas and highgrade transformation, and regarded under the category of 'metaplastic' carcinomas. 36,48,49 On the other hand, although many gallbladder adenosquamous carcinomas/squamous cell carcinomas showed highgrade histologic features, it may also be important to note that focal aberrant differentiation toward other cell lineages such as sebaceous differentiation and goblet cells (Figures 7 and 8) were also occasionally encountered in these tumors.…”

“…For example, in the breast and the pancreas, carcinomas with squamous differentiation have been shown to be aggressive neoplasia with a prognosis even worse than that of conventional adenocarcinomas of these respective sites. [33][34][35][36] Whether this is also valid for squamous cell carcinoma/adenosquamous carcinoma of gallbladder or not has yet to be proven.…”