Expression of p63 in Squamous Cell Carcinoma of the Lung and its Diagnostic Significance: A Meta-Analysis


  • Bibo Wang Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Yiping Han Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Jiajie Zang Department of Health Statistics and Center of Evidence-based Medicine, Second Military Medical University, Shanghai, China



p63, squamous cell carcinoma, lung cancer, meta-analysis, diagnose.


 Introduction: The expression of p63 has been studied in various tumor types, including squamous cell carcinoma (SCC). Methods and Results: Twenty-five trials met the inclusion criteria with a total of 1,193 patients. The overall positive proportion of p63 was 91.5% (95% CI, 86.3-94.8). Both histological and cytological methods of obtaining specimens showed a high expression of p63 in SCC at 89.8% (95% CI, 81.9-94.5) and 88.7% (95% CI, 80.9-93.6). The p63 positive proportion of the well or moderately differentiated subgroups was 92.7% (95% CI, 77.9-97.9) compared to the poorly differentiated subgroup at 86.9% (95% CI, 61.6-96.5). When using >1% of p63 immunoreactive cells as the positive standard, both sensitivity and specificity at 0.91 (95% CI, 0.86-0.94) and 0.80 (95% CI, 0.75-0.85), respectively, were acceptable. When using >10% and >50% standards, sensitivities of 0.92 (95% CI, 0.90-0.94) and 0.82 (95% CI, 0.78-0.85) and specificities of 0.84 (95% CI, 0.82-0.86) and 0.92(95% CI, 0.90-0.94) were shown. Conclusions: In SCC, there is a high expression of p63, which has no association with the histological or cytological methods used to obtain specimens or the degree of differentiation of the specimens. Even when only a small amount of cells were stained (>1%) as the positive standard, the sensitivity and specificity of p63 were maintained at a high level. We suggest that >50% of immunoreactive cells be used as the positive standard to achieve proper sensitivity and specificity.


Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin 2009; 59: 225-49.

Hoftman PC, Mauer AM, Voke EE. Lung cancer. Lancet 2000; 355: 479-85.

Liu Y, Sturgles CD, Grzybiekl DM. Microtubule associated protein a new sensitive and specified marker for pulmonary carcinomas and small cell carcinomas. Mod Pathol 2004; 14: 880-85.

Thomas PA, Plantadosl S, Postoperative T. Non-small cell lung cancer: squamous versus nonsquamous recurrences. J Thorax Cardiovasc Surg 1997; 94: 349-54.

Yang A, Kaghad M, Wang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 1998; 2: 305-16.

Charles J, Como D, Marshall J. p63 Expression Profiles in Human Normal and Tumor Tissues. Clin Cancer Res 2002; 8: 494-501.

Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088-101.

Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003; 326: 219.

Woodward M, Ed. Epidemiology: design and data analysis, 2nd ed. Boca Raton: Chapman and Hall/CRC Press.

Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003; 3: 25.

Pelosi G, Pasini F, Olsen SC, et al. p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas? J Pathol 2002; 198: 100-109.

Wang BY, Gil J, Kaufman D, Gan L, Kohtz DS, Burstein DE. p63 in Pulmonary Epithelium, Pulmonary Squamous Neoplasms, and Other Pulmonary Tumors. Human Pathol 2002; 33: 921-26.

Reis-Filho JS, Simpson PT, Martins A, Preto A, Gärtner F, Schmitt FC. Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 2003; 443: 122-32.

Massion PP, Taflan PM, Jamshedur RSM, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res 2003; 63: 7113-21.

Sheikh HA, Fuhrer K, Cieply K, Yousem S. p63 expression in assessment of bronchioloalveolar proliferations of the lung. Mod Pathol 2004; 17:1134-40.

Au NH, Gown AM, Cheang M, et al. p63 Expression in Lung Carcinoma A Tissue Microarray Study of 408 Cases. Appl Immunohistochem Mol Morphol 2004; 12: 240-47.

Camilo R, Capelozzi VL, Siqueira SA, Del Carlo Bernardi F. Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. Human Pathol 2006; 37: 542-46.

Zhang H, Liu J, Cagle PT, Allen TC, Laga AC, Zander DS. Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach. Mod Pathol 2005; 18: 111-18.

Wu M, Szporn AH, Zhang D, et al. Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers. Diag Cytopath 2005; 33: 223-27.

Shtilbans V, Szporn AH, Wu M, Burstein DE. p63 Immunostaining in destained bronchoscopic cytological specimens. Diag Cytopath 2005; 32: 198-203.

Nelson G. The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study. Mod Pathol 2006; 19: 417-28.

Kargi A, Gurel D, Tuna B. The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas. Appl Immunohistochem Mol Morphol 2007; 15: 415-20.

Robert T, Pang Y, Michael C. Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions. Diag Cytopath 2007; 36: 20-25.

Jorda M, Gomez-Fernandez C, Garcia M, et al. p63 differentiates subtypes of nonsmall cell carcinomas of lung in cytologic samples. Cancer Cytopath 2009; 46-50.

Shimada Y, Ishii G, Nagai K, et al. Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung. Cancer Sci 2009; 100: 2054-59.

Uke M, Rekhi B, Ajit D, Jambhekar N. The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de-stained bronchial lavage cytological smears. Cytopathology 2010; 21: 56-63.

Khayyata S, Yun S, Pasha T, et al. Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine-needle aspiration specimens. Diag Cytopath 2009; 37: 178-83.

Kim DH, Kwon M. Role of fine needle aspiration cytology, cell block preparation and CD63, p63 and CD56 immunostaining in classifying the specific tumor type of the lung. ACTA Cytologica 2010; 54: 55-59.

Moreira AL, Gonen M, Rekhtman N, Downey RJ. Progenitor stem cell marker expression by pulmonary carcinomas. Mod Pathol 2010; 23: 889-95.

Conde E, Angulo B, Redondo P, et al. The use of P63 immunohistochemistry for the identification of squamous cell carcinoma of the lung. PLoS ONE 2010; 5: 1-6.

Pereira TC, Share SM, Magalhães AV, Silverman JF. Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohistochemical tissue microarray study of 194 cases. Appl Immunohistochem Mol Morphol 2011; 19: 10-14.

Rekhtman N, Ang DC, Sima CS, Travis WD, Moreira AL. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol 2011; 1-12.

Noh S, Shim H. Optimal combination of immunohistochemical markers for subclassification of non-small cell lung carcinomas: A tissue microarray study of poorly differentiated areas. Lung Cancer 2011; 1-5.

Ocque R, Tochigi N, Ohori NP, Dacic S. Usefulness of immunohistochemical and histochemical studies in the classification of lung adenocarcinoma and squamous cell carcinoma in cytologic specimens. Am J Clin Pathol 2011; 136: 81-87.




How to Cite

Bibo Wang, Yiping Han, & Jiajie Zang. (2012). Expression of p63 in Squamous Cell Carcinoma of the Lung and its Diagnostic Significance: A Meta-Analysis. Journal of Cancer Research Updates, 1(2), 228–238.