Napsin A as a marker of clear cell ovarian carcinoma

BMC Cancer. 2013 Nov 5;13:524. doi: 10.1186/1471-2407-13-524.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Aspartic Acid Endopeptidases / genetics*
  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers, Tumor* / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • ROC Curve
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human