Case of the month - September 2006 - discussion

• 20-27% of Grade 3 invasive carcinomas of no special type (NST) will show a basal/myoepithelial phenotype on immunostaining.



• These tumours show a different metastatic pattern and (worse) clinical outcome from other grade 3 invasive ductal carcinomas



• The remaining 70-80% of NSTs are of a luminal phenotype



• 91% of a series of metaplastic carcinomas showed a basal phenotype on immunostaining (Reis-Filho 2006)



• > 50% of typical medullary carcinomas show a basal/myoepithelial phenotype (Jacquemier et al 2005)



• BRCA1 associated carcinomas frequently show a basal/myoepithelial phenotype:



• 5% of all breast cancers are BRCA-related
• Approximately 20% of breast carcinomas that are ER/PGR/Her2 negative and CK 5/6 positive will be associted with BRCA1 mutations
• There is a strong correlation between basal phenotype and reduced expression of BRCA proteins (Ribeiro-Silva et al 2005) (using immunohistochemistry)


• This is a further step along the path where neoplasms are defined increasingly by receptor status and/or marker phenotype in addition to morphology

Fulford (2006) and colleagues reviewed 453 grade 3 invasive ductal carcinomas of no special type. Using CK14 as a marker of basal differentiation they identified 88 positive tumours (20% of grade 3 carcinomas). These tumours commonly showed the following features:

• A prominent central scar



• Spindle cell differentiation or squamous metaplasia



• A high nucleo-cytoplasmic ratio



• A very high mitotic count - >40/10 hpf

Practice point:

We assess a tumour's receptor status on the core biopsy routinely requesting ER and Her2. If the tumour is Grade 3 and/or ER negative/ER poor (≤ Alred category 4) we also test for CK 5/6 as a screen for basal phenotype in addition to assessing PGR.

Note: For data on co-expression of luminal markers by myoepithelial phenotype carcinomas see Rakha et al 2006.

At present the subdivision of non-luminal ductal carcinomas of the breast into 'basal' and 'myoepithelial' is in the research domain rather than the subject of routine clinical practice. Nevertheless the subject is of very considerable interest and preliminary data suggest that true basal phenotype carcinomas have a poorer prognosis than myoepithelial phenotype carcinomas (Rakha et al 2006). 71% of this series of basal/myoepithelial carcinomas were grade 3 (compared with an overall figure of 48.5%) and 27% of all grade 3 carcinomas showed this basal/myoepithelial phenotype.

References:

1. Reis-Filho JS, Milanezi, Steele D et al
   Metaplastic breast carcinomas are basal-like tumours. Histopathology 2006;49:10-21.


2. Jacquemier J, Padovani L, Rabayrol L et al
   Typical medullary breast carcinomas have a basal/myoepithelial phenotype. J Pathol 2005;207:260-268



3. Ribeiro-Silva A; Ramalho LNZ, Garcia SB, Brandao DF, Chahud F & Zucoloto S.
   p63 correlates with bothe BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer. Histopathology 2005;47:458-66.



4. Fulford LG, Easton DF, Reis-Filho JS et al
   Specific morphological features predictive for the basal cell phenotype in grade 3 invasive ductal carcinoma of the breast. Histopathology 2006;49:22-34.



5. Rakha EA, Putti TC, Abd El-Rehim et al
   Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 2006;208:495-506.



6. Nielsen TO, Hsu FD, Jensen K et al
   Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma. Clinical Cancer Research 2004;10:5367-5374

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