Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium

Hum Pathol. 2015 Jul;46(7):957-62. doi: 10.1016/j.humpath.2015.03.008. Epub 2015 Apr 11.


Napsin A is a reliable marker for pulmonary adenocarcinoma and is expressed in a subset of ovarian clear cell carcinomas (O-CCCs), endometrial (EM) CCCs, and endometrioid carcinomas (EC). We investigated napsin A levels in O-CCC and EM-CCC and compared these with levels in other nonmucinous ovarian carcinomas and EM-EC, respectively. Napsin A, thyroid transcription factor (TTF)-1, paired box (PAX) 8, and cancer antigen (CA) 125 expression was evaluated in 111 ovarian and uterine carcinoma cases (22 O-CCC, 15 EM-CCC, 13 ovarian EC (O-EC), 39 high-grade serous carcinoma [HGSC], and 22 EM-EC) using immunohistochemistry. Napsin A immunoreactivity was observed in 21 (95.5%) of 22 O-CCC and 10 (66.7%) of 15 EM-CCC cases but was rare in O-EC and EM-EC (7.7% and 4.5%) and undetectable in HGSC cases. Thyroid transcription factor 1 was not expressed in O-CCC but was detected in 1 (6.7%) of 15 EM-CCC, 3 (23.1%) of 13 O-EC, 2 (5.1%) of 39 HGSC, and 1 (4.5%) of 22 EM-EC cases. All 111 cases examined were positive for PAX8, whereas 3 (20.0%) of 15 of EM-CCC and 1 (4.5%) of 22 EM-EC cases were negative for CA125. There were no napsin A/TTF-1 double-positive cases, except for 1 EM-CCC, in which cells had a focal expression pattern. All napsin A- and/or TTF-1-positive cases expressed PAX8 and CA125. In conclusion, napsin A is frequently expressed in O-CCC and EM-CCC, rarely in O-EC and EM-EC, and never in HGSC cases. These findings confirm the importance of using a panel of antibodies that includes napsin A, TTF-1, and PAX8 when evaluating metastatic carcinomas of unknown origin, particularly when gynecologic and pulmonary adenocarcinomas are included in the differential diagnosis.

Keywords: Clear cell carcinoma; Endometrial carcinoma; Napsin A; Ovarian carcinoma; PAX8.

Publication types

  • Comparative Study

MeSH terms

  • Aspartic Acid Endopeptidases / analysis*
  • Biomarkers, Tumor / analysis*
  • CA-125 Antigen / analysis
  • Carcinoma / enzymology*
  • Carcinoma / pathology
  • Diagnosis, Differential
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Membrane Proteins / analysis
  • Nuclear Proteins / analysis
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / analysis
  • Predictive Value of Tests
  • Thyroid Nuclear Factor 1
  • Transcription Factors / analysis


  • Biomarkers, Tumor
  • CA-125 Antigen
  • MUC16 protein, human
  • Membrane Proteins
  • NKX2-1 protein, human
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human