Clear cell carcinomas of the mullerian system: does the pathogenesis vary depending on their nuclear grade and their association with endometriosis? An immunohistochemical analysis

Abstract

Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis.

Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.

Figure 1

Ovarian low nuclear grade clear cell carcinoma showing p53 and Ki67 positivity (1(a): H&E 10x; 1(b): p53 10x; 1(c): Ki67 10x). Ovarian high nuclear grade CCC showing p53 and Ki67 positivity (1(d): H&E x 20x; 1(e): p53 20x; 1(f): Ki67 20x). Ovarian HNG CCC negative for p53 but positive for Ki67 (1(g): H&E 20x; 1(h): p53 20x; 1(i): Ki67 20x).

Figure 2

Ovarian low nuclear grade CCC associated with endometriosis showing negative staining for p53 but positive staining for Ki67 (2(a): H&E 4x; 2(b): H&E 10x; 2(c): p53 10x; 2(d): Ki67 10x).

Figure 3

Endometrial low nuclear grade CCC with adenomyosis showing negative staining for p53 and positive staining for Ki67 (3(a): CCC H&E 10x; 3(b): adenomyosis H&E 10x; 3(c): p53 10x; 3(d): Ki67 10x).