Differential immunohistochemical and biological profile of squamous cell carcinoma of the breast.

Background: Pure or metaplastic squamous cell carcinoma (SCC) of the breast is a rare entity with an unclear pathogeny and aggressive clinical behaviour. An attempt was made to characterize its differential immunohistochemical and biological profile. Patients and Methods: Twenty-seven cases of SCC (pure or not) of the breast were matched with 27 ductal invasive carcinomas (IDC) for age, tumour size, nodal involvement and year of diagnosis. The expression levels of oestrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), HER2, Cyclin B1, hTERT, cytokeratins (CK) 5/6 and p63 were determined immunohistochemically in both cohorts. The presence of the human papilloma virus (HPV) genome was investigated by polymerase chain reaction (PCR). Results: Pure and metaplastic SCC displayed common profiles typifying a basal origin: they never expressed ER or PR, were HER2-negative in 93% of cases, exhibited positivity for CK5/6 or EGF-R in 75% and 85%, and for p63 in 70% of cases and were highly proliferative. These profiles were markedly different from those of matched controls (p<0.001 for five markers) except for HER2 and hTERT. The HPV genome was detected in 2 out of 14 cases (14%) of SCC. Conclusion: The expression profile of SCC of the breast was markedly different from that of IDC. A typical "basal-like" phenotype was displayed that may explain part of their behaviour and justify specific therapeutic approaches. HPV infection was not a leading oncogenic event in SCC of the breast. Recent data derived from micro-array analyses and extended to immunohistochemical classifications have tended to subclassify breast carcinomas, according to their expression of a subset of markers, into at least six categories: Her-2 overexpressing, basal-like, luminal type A, B and C, and normal-like breast cancers (1-3). Further data have shown that these newly described groups may display very different clinical behaviours and sensitivity to drugs (4, 5). Such classification therefore appears to be a potentially promising tool for therapeutic targeting of localized or advanced breast cancer. Pure squamous cell carcinoma (SCC) of the breast is a very rare malignancy. It accounts for less than 0.1% of all breast carcinomas, while carcinoma with squamous metaplasia accounts for 3.7% (6-11). The pathology of SCC of the breast remains unclear although it has been suggested that it may originate from squamous metaplasia of the ductal epithelium. However, squamous metaplasia may arise from myoepithelial cells (12). These tumours are rather aggressive (10). Most of them are negative for estrogen (ER) and progesterone (PR) receptors, but a detailed immunohistochemical profile is unknown. In an attempt to better characterise and understand this particular entity and to determine whether or not it could be classified within one of the particular breast cancer subgroups recently described, the pathological and biological features of pure or largely metaplastic squamous cell carcinoma of the breast were analysed. These tumours were compared to 27 matched cases of invasive ductal carcinoma (IDC) by immunohistochemistry, for the expression of ER and PR, epidermal growth factor receptor (EGFR),