Cluster 3 includes patients with worse overall survival and more poorly-differentiated whereas those in cluster 1 were more well-differentiated and had a more favorable outcome.
Its distribution is similar in mammary tumors, at least in more well-differentiated ones.
Recently, a positive correlation between IRS-1 nuclear expression and a more well-differentiated, non-metastatic phenotype for ductal breast cancer was reported [ 46].
The vast majority of ER + breast cancers are clearly also AR + (84 to 91%) [ 5, 37, 38] and patients with tumors that co-express AR with ER and PR have a longer DFS than those with tumors negative for all three receptors [ 37], probably reflecting a more well-differentiated state than that of receptor-negative tumors.
Transfection of miR-200c mimic into the dedifferentiated breast and endometrial cancer lines (BT549, MDA-MB-231, Hec50 and AN3CA) results in levels of mature miR-200c comparable to endogenous levels in the more well-differentiated breast and endometrial cancer lines (MCF7 and Ishikawa).
Conversely, experimental in vitro data indicate that Stat5a maintains cellular differentiation and suppresses epithelial-to-mesenchymal transition and invasive characteristics of human breast cancer cell lines [ 20- 23], and a positive association between nuclear Stat5a and more well-differentiated human breast cancer has been reported [ 24, 25].
Smaller tumors occurred more often than larger tumors (T1 + 2 versus T3 + 4; 70.1% versus 29.8%), higher tumor stages were more frequent than lower tumor stages (I, II versus III, IV, 28.3% versus 71.6%), and tumors were also more commonly well differentiated (G1, 2 versus G3, 70.2% versus 29.8%).
It has been proposed alternatively that a proportion of these low-grade invasive tumours might de-differentiate over time into more aggressive, less well differentiated tumours (Tabár et al., 1999), although this was not found in another screening programme (Hakama et al., 1995).
Other common symptoms are chest pain, dyspnoea, pleural effusion (more common in well differentiated papillary MM, localised MM, epithelioid haemangioendothelioma and desmoplastic small round cell tumour of the pleura), in relation to their possible malignant behaviour, with invasion of the chest wall, mimicking the typical symptoms of a classic MM.
