E-cadherin expression in renal cell cancer and its significance in metastasis and survival

Abstract

Sumary Decreased expression of E-cadherin (E-CD). a homotypic intercellular adhesion molecule, is considered to elicit detachment of tumour cells from primary lesions, which is the first stage of metastasis. Since renal cell cancer (RCC) shows a relatively high frequency of metastasis, we focused our interest on E-CD expression in RCC and its clinicopathological implications. We examined E-CD expression in normnal kidney and RCC by immunohistochemical staining. In normal kidney, E-CD expression was localised in distal tubules and collecting ducts. In RCC, 20 of 106 primary lesions (18.9%) expressed E-CD. whereas none showed positive staining for eight metastatic lesions. There was a statistically significant correlation between loss of E-CD expression and advanced stages of RCC. Kaplan-Meier analysis showed better prognosis in the group with preserved E-CD expression than without E-CD expression (Cox -Mantel test. P = 0.022, the average follow-up was 32 months or until death). This study suggests that the patients with decreased E-CD expression may be associated with metastasis, resulting in poor prognosis. However, frequency of E-CD expression in RCC is lower than in other cancers, which may be derived from the localised distribution of E-CD expression in normal kidney.Keywords E-cadherin; renal cell cancer: metastasis It is well known that cadherins, a family of Ca2+-dependent intercellular adhesion molecules, play essential roles in organogenesis and in the maintenance of normal structure and function (Behrens et al., 1985;Eidelman et al., 1989;Takeichi, 1991). Recently, E-cadherin (E-CD), a subclass of cadherins, has come to be considered to be important as an inhibitory factor in metastasis (Behrens et al., 1985; Frixen et al., 1991;Takeichi, 1991 (1991) showed that loss of E-CD can generate an invasive phenotype, which can be prevented by transfection with E-CD cDNA. Clinically, the correlation between decreased E-CD expression and advanced stages or dedifferentiation was also reported in a variety of tumours (Frixen et al., 1991;Shiozaki et al., 1991; Oka et al., 1992;Umbas et al., 1992;Bringuier et al., 1993; Oka et al., 1993;Terpe et al., 1993). However, reports in relation to the prognosis of malignant tumours have been rare until now (Bringuier et al., 1993 Immunohistochemical staining Anti-E-CD monoclonal antibody (HECD-1, Takara Biomedicals, Tokyo, Japan) was used in this study, and immunoperoxidase staining was performed by modifying the streptavidin-biotin bridge technique described previously (Katagiri et al., 1993

Expression of Ksp-cadherin during kidney development and in renal cell carcinoma

“…Therefore, lack of Ksp-cadherin protein expression in RCC tumour tissues seems to be in accordance with the origin of the tumours. However, expression of E-cadherin on RCC tumour cells, which due to the origin must be regarded as an aberrant expression pattern, can be correlated with tumour stages but not with survival rates (Katagiri et al, 1995;Shimazui et al, 1997). It will be a challenge for the near future to determine in a larger cohort of patients whether the expression of Ksp-cadherin mRNA can also be correlated with different tumour stages or survival rates.…”

Levels of angiogenesis and expression of angiogenesis‐related genes are prognostic for organ‐specific metastasis of renal cell carcinoma

“…Therefore, reduced levels of E-cadherin expression would facilitate a decrease in cellular and tissue differentiation and result in a higher pathologic grade. Katagiri et al 26 found that the frequency of E-cadherin expression in RCC is lower than in other cancers. This may be due to the more localized distribution of E-cadherin expression in the normal kidney compared with other organs.…”

“…Low levels of E-cadherin have been reported previously to be associated with an increased risk for the development of metastasis in human tumors, [55][56][57] including RCC. 26 E-cadherin is a calcium-dependent cell adhesion molecule that is important in cell-cell interactions in the epithelium and thus plays a major role in organizing and maintaining the structure and integrity of epithelial sheets. Cell detachment is one of the necessary steps in the process of metastasis.…”

“…Most hypervascularized RCCs also express a number of angiogenesis-related factors. To assess the prognostic value for RCC, the expression levels of various angiogenesis-related genes, including basic fibroblast growth factor (bFGF), 14 -18 vascular endothelial cell growth factor (VEGF), [17][18][19][20][21] interleukin-8 (IL-8), 22 matrix metalloproteinase types 9 (MMP-9) [23][24][25] and 2 (MMP-2), , and E-cadherin 26,27 have been studied. The ratio of MMPs (MMP-9 and MMP-2) to E-cadherin (M/E ratio) recently was reported to be an important prognostic factor for several cancers, including pancreatic carcinoma, 28 nonsmall cell lung carcinoma, 29 prostate carcinoma, 30 bladder carcinoma, 31 and RCC.…”

Establishment and Validation of Real-Time Polymerase Chain Reaction Method for CDH1 Promoter Methylation

“…Inactivation of these genes are hypothesized to be an important step in the progression from tumor formation to invasion and metastasis. 10 These genes and some other cadherin family members are located on the long arm of chromosome 16 (16q), 11 a chromosomal location that is frequently deleted in breast and other types of carcinomas. [12][13][14][15][16] On the basis of Knudson's 17 "two-hit" hypothesis, both alleles of tumor suppressor genes have to be inactivated for loss of expression.…”