p40 exhibits better specificity than p63 in distinguishing primary skin adnexal carcinomas from cutaneous metastases

Hum Pathol. 2014 May;45(5):1078-83. doi: 10.1016/j.humpath.2014.01.006. Epub 2014 Jan 28.

Abstract

The histopathologic distinction between primary adnexal carcinomas and metastatic adenocarcinoma to the skin from sites such as the breast, lung, and others often presents a diagnostic dilemma. Current markers of diagnostic utility include p63 and cytokeratin 5/6; however, their expression has been demonstrated in 11% to 22% and 27% of cutaneous metastases, respectively. Furthermore, the immunoreactivity of p40 and GATA3 in various cutaneous adnexal carcinomas has not been previously reported. In the present study, we compared the expression of p40, p63, cytokeratin 5/6, and GATA3 in a total of 143 cases, including 67 primary adnexal carcinomas and 76 cutaneous metastases. p40, p63, cytokeratin 5/6, and GATA3 expression was observed in 80%, 84%, 86%, and 47% of primary adnexal carcinoma, respectively, and in 8%, 17%, 26%, and 40% of cutaneous metastases, respectively. χ(2) Analysis revealed statistically significant P values (<.0001) for p40, p63, and cytokeratin 5/6 in distinguishing primary adnexal carcinoma from cutaneous metastases. In summary, while p63 and cytokeratin 5/6 have similar sensitivity (84% and 86%, respectively) in detecting primary adnexal carcinomas, p40 appeared to be the most specific marker (92%) with the best positive predictive value (90%). Since breast and lung are the most common sites of origin for cutaneous metastases, p40 is the best distinguishing marker in these settings. None of the four studied markers (p40, p63, cytokeratin 5/6, and GATA3) are helpful in distinguishing between primary adnexal carcinomas from cutaneous metastases of salivary gland or bladder malignancies.

Keywords: Adnexal neoplasm; Cutaneous metastasis; Cytokeratin 5/6; p40; p63.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / secondary
  • Biomarkers, Tumor / metabolism
  • Female
  • GATA3 Transcription Factor / biosynthesis
  • Humans
  • Keratin-5 / biosynthesis
  • Keratin-6 / biosynthesis
  • Membrane Proteins / biosynthesis*
  • Sensitivity and Specificity
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / pathology
  • Skin Neoplasms / secondary*
  • Transcription Factors / biosynthesis
  • Tumor Suppressor Proteins / biosynthesis

Substances

  • Biomarkers, Tumor
  • CKAP4 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Keratin-5
  • Keratin-6
  • Membrane Proteins
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins