Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study

Abstract

IntroductionSome molecular subtypes of breast cancer have preferential sites of distant relapse. The protein expression pattern of the primary tumor may influence the first distant metastasis site.MethodsWe identified from the files of the Finnish Cancer Registry patients diagnosed with breast cancer in five geographical regions Finland in 1991-1992, reviewed the hospital case records, and collected primary tumor tissue. Out of the 2,032 cases identified, 234 developed distant metastases after a median follow-up time of 2.7 years and had the first metastatic site documented (a total of 321 sites). Primary tumor microarray (TMA) cores were analyzed for 17 proteins using immunohistochemistry and for erbB2 using chromogenic in situ hybridization, and their associations with the first metastasis site were examined. The cancers were classified into luminal A, luminal B, HER2+ enriched, basal-like or non-expressor subtypes.ResultsA total of 3,886 TMA cores were analyzed. Luminal A cancers had a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases. Primary tumors that gave first rise to bone metastases expressed frequently estrogen receptor (ER) and SNAI1 (SNAIL) and rarely COX2 and HER2, tumors with first metastases in the liver expressed infrequently SNAI1, those with lung metastases expressed frequently the epidermal growth factor receptor (EGFR), cytokeratin-5 (CK5) and HER2, and infrequently progesterone receptor (PgR), tumors with early skin metastases expressed infrequently E-cadherin, and breast tumors with first metastases in the brain expressed nestin, prominin-1 and CK5 and infrequently ER and PgR.ConclusionsBreast tumor biological subtypes have a tendency to give rise to first distant metastases at certain body sites. Several primary tumor proteins were associated with homing of breast cancer cells.

DLC1-dependent parathyroid hormone–like hormone inhibition suppresses breast cancer bone metastasis

“…In addition, we observed an organ-specific correlation of DLC1 expression with bone metastasis. Interestingly, we also found in the NKI dataset that DLC1 silencing was associated with bone metastasis only for luminal-type breast tumors (Supplemental Figure 9G), which are known to be predisposed to bone recurrence (42,43), although such findings need to be validated in additional datasets. Previous studies have shown the association of DLC1 silencing with poor prognosis in breast cancer (15).…”

Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon?

“…Further, expression levels of the panel of 17 well-justified proteins and their potential associations with the first metastatic site were investigated in the study utilising the data of 2032 BC patients in Finland [31]. Corresponding results revealed the breast tumours that linked to BM do frequently express cytokeratin-5 (P < 0.05), prominin-1 (P < 0.05), nestin (P < 0.1), smooth muscle actin (P < 0.1) being more often ER and PR negative (P < 0.05).…”

Stromal expression of matrix metalloproteinase 2 in cancer-associated fibroblasts is strongly related to human epidermal growth factor receptor 2 status in invasive breast carcinoma

“…Several recent studies support the hypothesis that, in invasive breast carcinoma, the gene expression profile of the epithelial component and, therefore, the immunohistochemical profile surrogates of molecular classes, represent biologically distinct diseases with different response to therapy and clinical outcome (12,13). In addition to the epithelial cell autonomous processes, it has been hypothesized that the tumor microenvironment, and particularly CAFs, are able to promote tumor cell proliferation, angiogenesis and metastasis (3,4,14).…”