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Abstract

The purpose of this study was to immunocytochemically investigate two new markers, the sigma-1 receptor and the human sterol isomerase (hSI), in comparison with a series of clinicopathological and immunocytochemical prognostic factors in a trial including 95 patients with operable primary breast cancers. Our results showed no statistically significant relationship between these two markers and the age of the patients, their menopausal status, the tumour size and its histological grade, the nodal status and the expression of the Ki-67 proliferative marker. However, we evidenced a close correlation between the sigma-1 receptor expression and the hormonal receptor positivity ( P = 0.008), essentially due to a link with the progesterone receptor status ( P = 0.01). By contrast there was an inverse relationship between hSI expression and the oestrogen receptor and/or progesterone receptor positivity ( P = 0.098). A significant relationship was shown between both the sigma-1 receptor, hSI expressions and Bcl2 expression, with P = 0.017 and 0.035 respectively. We also assessed whether the expression of the sigma-1 receptor or hSI might be linked with disease-free survival (DFS) and found that the presence of hSI and the absence of sigma-1 receptor expression were associated with a poorer disease-free survival ( P = 0.007). Altogether these results suggest that in primary breast carcinomas in association with the evaluation of the steroid receptor status, the sigma-1 receptor and hSI may be interesting new markers useful to identify those patients who might be able to benefit from an adjuvant therapy. © 2000 Cancer Research Campaign

Sigma receptors [σRs]: biology in normal and diseased states

“…Using N -[2-(1′-piperidinyl)- ethyl]-3-123I-iodo-4 methoxybenzamide, also moderately selective for σ 1 Rs, another study also found that σ 1 Rs and σ 2 Rs were present at high density on human breast tumor biopsies but virtually absent in normal tissues ( 980 ). Expression of the σ 1 R, monitored immunocytochemically, has been suggested as a possible marker for predicting the aggressiveness of breast tumors, in particular, where there was a significant correlation between σ 1 R expression and PROG receptor status ( 1028 , 1029 ). The age-related decrease in PROG may be important in the binding of σ 1 R agonists in tumor cells ( 759 ).…”

Sigma 1 Receptor is Overexpressed in Hepatocellular Adenoma: Involvement of ERα and HNF1α

“…A specific SigR1 antibody showed a high level of SigR1 in lung, breast, and prostate cancer cell lines compared to the basal level [ 11 ]. However, the role of SigR1 in cancer is not clear as some studies showed that silencing SigR1 by siRNA in human breast cancer cell line significantly reduced cell proliferation [ 11 ], while other reports suggest that SigR1 could inhibit tumor growth [ 12 , 13 ]. Likewise, it has been reported that the level of expression of SigR1 was related to the aggressiveness of cancer: the more SigR1 is expressed, the more aggressive the tumor is [ 11 , 14 ].…”

“…Likewise, it has been reported that the level of expression of SigR1 was related to the aggressiveness of cancer: the more SigR1 is expressed, the more aggressive the tumor is [ 11 , 14 ]. In contrast, Simony-Lafontaine et al established that in human breast tumors, the level of SigR1 was correlated to patient survival, suggesting that SigR1 inhibits tumor growth [ 12 ] and more recently, a decrease in the expression of SigR1 in Hepatocellular carcinoma [ 15 ] has been shown. Nevertheless, many studies show the involvement of SigR1 in cancer [ 16 , 17 ], and, for example, SigR1 has been suggested as a potential prognosis and diagnostic marker for breast tumors [ 12 ] and prostate cancers [ 18 ].…”

“…In contrast, Simony-Lafontaine et al established that in human breast tumors, the level of SigR1 was correlated to patient survival, suggesting that SigR1 inhibits tumor growth [ 12 ] and more recently, a decrease in the expression of SigR1 in Hepatocellular carcinoma [ 15 ] has been shown. Nevertheless, many studies show the involvement of SigR1 in cancer [ 16 , 17 ], and, for example, SigR1 has been suggested as a potential prognosis and diagnostic marker for breast tumors [ 12 ] and prostate cancers [ 18 ]. Interestingly, in breast and prostate tumors, the SigR1expression is respectively related to progesterone and androgen status [ 11 , 12 ] suggesting a potential role of these hormones on the expression of SigR1.…”

“…Nevertheless, many studies show the involvement of SigR1 in cancer [ 16 , 17 ], and, for example, SigR1 has been suggested as a potential prognosis and diagnostic marker for breast tumors [ 12 ] and prostate cancers [ 18 ]. Interestingly, in breast and prostate tumors, the SigR1expression is respectively related to progesterone and androgen status [ 11 , 12 ] suggesting a potential role of these hormones on the expression of SigR1.…”