Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis

Abstract

Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.

Overexpression of Claudin-1 is Associated with Advanced Clinical Stage and Invasive Pathologic Characteristics of Oral Squamous Cell Carcinoma

“…Claudin-1 is perhaps the most studied protein among claudin family members. The reduced expression of claudin-1 was observed in breast and prostate cancers [10][11][12], however, a greater number of other cancers including gastric, thyroid, pancreatic, urothelial and cervical cancers instead showed increased claudin-1 expression [13][14][15][16]. This suggests that this protein may have tissue-specific functions and its roles in various cancers may be different depending on the type of cancer cells and/or the nearby cancer environment.…”

“…A number of studies reported the overexpression of claudin-4 in a variety of cancers [12,14,[17][18][19][20][21][22][23]. The claudin-4 up-regulation was shown to stimulate MMP-2 activity in ovarian carcinoma cells and promote cancer invasion [36].…”

“…Their levels of expression appear to be distinctly variable depending on the type of cancers. The claudin-1 expression was shown to be down-regulated in breast and prostate cancers [10][11][12], whereas its overexpression was observed in gastric, thyroid, pancreatic, urothelial and cervical cancers [13][14][15][16].…”

“…The claudin-4 expression was up-regulated in several cancers, including esophageal, gastric, colorectal, pancreatic, ovarian, urothelial, breast, endometrial and prostate cancers [12,14,[17][18][19][20][21][22][23]. Its role in the invasiveness and survival of ovarian cancer cells has also been suggested in an in vitro study [24].…”

Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer

“…Among the proteins analyzed in order to determine the association of its expression with the different phenotypes of breast cancer, claudin-7 expression was noteworthy, as a decreased expression of claudin-7 correlated with higher tumor grade and metastatic disease (32). Moreover, the claudin low subtype, which has recently emerged in the molecular classification of breast cancer, is characterized by reduced expression of claudins including claudin-7 (6).…”