乳がんのCTCとケラチンの関係

Circulation tumor cells (CTCs) are metastatic bio-marker of breast cancer metastasis.

Previously, cancer cells are known to be separated from tumor mass, when the breast cancer progresses.
Therefore, CTCs is derived from epithelia and expresses the epithelial marker protein at cell membrane.

On the other hand, breast cancer are thought to be categorized by 4 or 5 subtypes.
These categories are luminal A, luminal B, HER2-enriched, triple negative and basal-like/Claudin-low.
The difference between basal-like and Claudin-low is well researched recently, but critical bio-markers have not been found yet.

This paper might show the possibility that the keratin expression differs from each subtypes.

Changes in Keratin Expression during Metastatic Progression of Breast Cancer: Impact on the Detection of Circulating Tumor Cells
Purpose: Circulating tumor cells (CTC) might function as early markers for breast cancer metastasis or monitoring therapy efficacy. Enrichment and identification of CTCs are based on epithelial markers that might be modulated during epithelial–mesenchymal transition. Little is known about the expression of keratins in CTCs and whether all CTCs can be detected with antibodies directed against a limited panel of keratins.

Experimental Design: Protein expression of keratin 2, 4–10, 13–16, 18, and 19 were assessed by a cocktail of antibodies (C11, AE1, AE3, and K7) and keratin antibodies C11 and A45-B/B3 alone in 11 breast cancer cell lines and 50 primary breast carcinomas and their lymph node metastases. Furthermore, CTCs were assessed in blood of 70 metastatic breast cancer patients.

Results: Claudin-low cell lines did not show expression of normal breast epithelial keratins but were positive for K14 and K16, detected by the cocktail only. Primary breast carcinomas showed changes in keratin expression during metastatic progression to the lymph nodes. In 35 of 70 patients CTCs were identified, of which 83%, 40%, and 57% were identified by the cocktail, C11 and A45-B/B3, respectively. Identification of CTCs by the cocktail was associated with shorter survival (P < 0.01). In silico analyses revealed association between KRT16 expression and shorter relapse-free survival in metastatic breast cancer.

Conclusion: Breast cancer cells show a complex pattern of keratin expression with potential biologic relevance. Individual keratin antibodies recognizing only a limited set of keratins inherit the risk to miss biologically relevant CTCs in cancer patients, and antibody cocktails including these keratins are therefore recommended. Clin Cancer Res; 18(4); 993–1003. ©2012 AACR.

Changes in Keratin Expression during Metastatic Progression of Breast Cancer: Impact on the Detection of Circulating Tumor Cells | Clinical Cancer Research

We maybe have to consider the breast cancer subtype when we diagnose the metastasis by CTCs detection.