Napsin A as a marker of clear cell ovarian carcinoma

open access

Background

Clear cell carcinomas are aggressive tumors with a distinct biologic behaviour. In a genome-wide screening for genes involved in chemo-resistance, NAPA was over-expressed in cisplatin-resistant cells. The NAPA (protein) Napsin A was described to promote resistance to cisplatin by degradation of the tumor suppressor p53.

Methods

Totally 131 patients were included in this study all in FIGO-stages I-II; 16 were clear cell tumors which were compared with 40 Type I tumors and 75 type II tumors according to the markers Napsin A, p21, p53 and p27 and some clinical features. For detection of the markers tissue microarrays and immunohistochemistry were used.

Results

Positivity for Napsin A was detected in 12 (80%) out of the 15 clear cell tumors available for analysis compared with 3 (4%) out of the Type I and II tumors in one group (p < 0.001). Differences in p21 status, p53 status, and p21 + p53- status were striking when clear cell tumors were compared with Type I, Type II, and Type I and II tumors in one group, respectively. The p21 + p53-status was associated to positive staining of Napsin A (p = 0.0015) and clear cell morphology (p = 0.0003). In two separate multivariate logistic regression analyses with Napsin A as endpoint both clear cell carcinoma with OR = 153 (95% C.I. 21--1107); (p < 001) and p21 + p53- status with OR = 5.36 (95% C.I. 1.6-17.5); (p = 0.005) were independent predictive factors. ROC curves showed that AUC for Napsin A alone was 0.882, for p21 + p53- it was 0.720 and for p21 + p53-Napsin A + AUC was 0.795. Patients with clear cell tumors had lower (p = 0.013) BMI than Type I patients and were younger (p = 0.046) at diagnosis than Type II patients. Clear cell tumors had a higher frequency (p = 0.039) of capsule rupture at surgery than Type I and II tumors.

Conclusions

Positivity of Napsin A in an epithelial ovarian tumor might strengthen the morphological diagnosis of clear cell ovarian carcinoma in the process of differential diagnosis between clear cell ovarian tumors and other histological subtypes.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

"...Our findings related to the clinico-pathological differences are supported by earlier studies[4,7,10] but results about the immunohistochemical profile for Napsin A is new. Clear cell carcinomas resembles Type I tumors based on relative genetic stability and

frequent presentation in stage I, but on the other hand, clear cell carcinoma is high grade at diagnosis. Furthermore, wild-type p53 is mostly present and mutations are uncommon in clear cell tumors contrary to Type II tumors, which are genetically unstable and have a highrequency of p53 mutations [10,11]. Ovarian clear cell carcinomas constitute a heterogeneous disease at the genomic level despite having similar histological

features. Previous data fromTan et al [11] has suggested that the pattern of genome-wide copy number aberrations may predict clinical outcome...