The expression of CK7 was different between CRCC and “non-clear cell” RCC subtypes; 84.2% of “non-clear cell” RCCs (ChRCC, PRCC) were found CK7 positive, while expression rate was 27.4% (17 of 62 tumors) for CRCCs (p=0.001). Of 13 PRCCs, 10 were found to be CK7 positive (%76.9) while, all ChRCCs were immunoreactive for CK7 (100%). The expression of CK7 was 100% and 62.5% (5 of 8 tumors) in PRCCT1 and PRCCT2, respectively (Table 2). In ChRCC, and PRCC the CK7 immunoreactivity was diffuse and strong throughout the cytoplasm and in the cell membranes of the tumor cells (Figure 1), whereas the distribution was patchy with strong reactivity in CRCC (Figure 2a, b). The immunoreactivity of CK7 in RO was noted in 4 of 6 tumors that was found only in scattered cells (Figure 2c, d). RO was entirely CK20 negative. CK20 was widely negative in RCC subtypes. Out of 62 CRCCs, 3 tumors were CK20 immunoreactive (4.8%) while only 1 PRCCT2 was positive (5.2%) in the group of “non-clear cell” RCCs (1 of 19 tumors). In unclassified RCC group, one of the two tumors was positive for CK7 and all were negative for CK20. CK10 was entirely negative in all tumor subtypes.
Table 2: Relation of CK7 and CK20 expression with RCC subtypes.
As shown in Table 3, CK7 expression was related with nuclear differentiation in RCCs (p=0.039). CK7 was positive in 52.5% of the LNG and 30.2% of HNG tumors. Higher percentage (61.8%) of CK7 positive tumors showed LNG differentiation.
Table 3: CK7 expression rates in RCC subtypes in relation with nuclear grades.
CK7 immunoreactivity in PRCC has commonly been reported with differing staining rate and intensity in type 1 and 2 tumors [13],[14]. Both studies have revealed a strong expression of the marker in the relatively benign PRCCT1, compared with the weak expression in the more agressive type 2 tumors. In the present study, CK7 was immunoreactive in total of 5 PRCCT1 tumors and 5 of 8 PRCCT2 tumors with a diffuse pattern and strong intensity. Although this diffuse and strong expression of CK7 in PRCCT2 is not consistent with the previous reports, the present study revealed a significant correlation between CK7 expression and nuclear differentiation (p=0.039), which supports the relation of CK7 expression with tumor aggressiveness. CK7 was expressed in 52.5% (20 of 39 tumors) of the tumors with LNG, and 30.2% [13] of 42 tumors) of the tumors with HNG. This strong association may be the reason for the conflicting results in the literature for the differentiation of RCC subtypes. We may refer that if CK7 expression is compared between the subtypes with the same NG, more significant and persuading results would be achieved, and it would be more meaningful in diagnosing tumor subtypes, regardless of negative impact of cellular differentiation.
CK20 has been shown to have a limited expression in normal tissues and neoplasms. CK20 expression in renal tubular epithelial tumors has been seldomly reported, and identified in 0-7.7% of RCCs [9],[14],[15],[19]. Langner et al [14] have reported a general lack of CK20 expression in a series of 233 renal tumors, with a positivity in only 2 of 8 PRCCT2s. Kim et al [9] have observed CK20 immunoreactivity in 4 of 20 PRCCs, without indicating their subtypes. Both studies have revealed the absence of CK20 in RO [9],[14]. Our results are similar to those found in these reports in that we detected only one PRCCT2 showing CK20 expression, and negativity for all cases with RO. But in our series in a total of 62 CRCCs, more than 50% of cells of 3 tumors were moderately stained with CK20. This confusing result shows the possibility of positive CK20 expression in CRCC. Literature findings have also shown confusing results for RO, and paucity of studies have reported CK20 expression in Ross. Stopyra et al have found the coordinate staining of CK7 and CK20 as a useful diagnostic tool in distinguishing RO from RCC [20]. In our opinion, CK20 does not appear to show a consistent immunoreactivity neither in RCC nor in RO, and does not seem to be a reliable differentiating marker for renal tubular neoplasms.
Literature contains scarce number of reports for CK10 expression in renal epithelial tumors which absolutely have shown the absence of the marker [14]. None of the tumors in our study had immunoreactivity with CK10, as well. Thus CK10 seems to have no role in renal epithelial tumor differentiation.
We conclude that, CK7 immunohistochemistry is a useful diagnostic tool in distinguishing “non-clear” RCC from CRCC with diffuse and strong expression of CK7 supporting “nonclear” RCC diagnosis. The extent of CK7 expression may indicate the aggressiveness of the tumor, and with this regard, better organized studies consisting of larger series of RCCs with the same NG are needed to be evaluated. CK20 and CK10 immunohistochemistry seem to be an unreliable analytical method in differentiating renal tubular neoplasms.
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