• Reno Keumalazia Kamarlis Department of Pathology Anatomy, Medical Faculty, Syiah Kuala University, Banda Aceh, Indonesia.
  • Muhammad Nadjib Dahlan Lubis Department of Pathology Anatomy, Medical Faculty, Sumatera Utara University, Medan, Indonesia.
  • Bethy S Hernowo Department of Pathology Anatomy, Medical Faculty, Padjajaran University,Bandung, Indonesia.
  • Azmi S Kar Department of Internal Medicine, Medical Faculty, Sumatera Utara University, Medan, Indonesia.
  • Basri A Gani Department of Biology Oral, Dentistry Faculty, Syiah Kuala University, Banda Aceh-Indonesia, Indonesia.


 Objective: To assess the immune expressions of cytoplasmic and nuclear protein63 (p63) proteins in metaplastic triple-negative breast cancer (TNBC) patients with basal-like and non-basal-like types based on age.

Methods: Forty samples of breast cancer patients diagnosed with TNBC were examined immune histochemical based on the immune expressions of cytoplasmic and nuclear p63 with basal-like (CK 5/6, positive) and non-basal-like (CK 5/6 negative) types. The histoscore values were categorized into Score 1 (<20%, negative), Score 2 (>20% - 50%, weak positive), Score 3 (>50% - 80%, moderate positive), and Score 4 (>80 %, strong positive) also analyzed by one-way analysis variance, probability (p<0.05), and correlation (p<0.01).

Results: Forty subjects with breast cancer showed 23 of basal-like (57.5%) and 17 of non-basal-like (42.5%) types. The cytoplasmic p63 had a low histoscores in the group of < 40–49 years old (55%), the moderate group of 40–55 years old (27.5%), and the high group of fewer than 50–60 years old (17.5%). The nuclear p63 was low in all age groups (p<0.05). It was the significant difference between basal-like and non-basal-like types (p<0.01) and strongest correlation (1.00). The immunoexpression of cytoplasmic p63 of basal-like cell type had an intensity of 88.2%, while nuclear p63 possessed 11.8% (p<0.05).

Conclusion: The frequency of cytoplasm p63 in all age groups of metaplastic breast cancer of basal-like type was more dominant than the nuclear p63. Otherwise, in the non-basal-like type, the cytoplasmic p63 protein was lower than the of nuclear p63 protein.

Keywords: Cytoplasmic protein63, Nuclear protein63, Metaplastic breast cancer, Basal-like, Non-basal-like.

Author Biography

Reno Keumalazia Kamarlis, Department of Pathology Anatomy, Medical Faculty, Syiah Kuala University, Banda Aceh, Indonesia.
Department of Oral Biology, Dentistry Faculty, Syiah Kuala University


1. Elgadir MA, Salama M, Adam A. Anti-breast cancer from various natural sources, review. Int J Pharm Pharm Sci 2015;7:44-7.
2. Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz U, Harbeck N. Triple-negative breast cancer - Current status and future directions. Ann Oncol 2009;20:1913-27.
3. Jayakumar S, Haridass S, Krishnamurthy V. Anticancer activity of Punica Granatum rind extracts against human lung cancer cell line. Asian J Pharm Clin Res 2012;5 Suppl 2:204-10.
4. Boyle P. Triple-negative breast cancer: Epidemiological considerations and recommendations. Ann Oncol 2012;23 Suppl 6:vi7-12.
5. Zaha DC. Significance of immunohistochemistry in breast cancer. World J Clin Oncol 2014;5:382-92.
6. Su X, Chakravarti D, Flores ER. p63 steps into the limelight: Crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer 2013;13:136-43.
7. Ferronika P, Triningsih FX, Ghozali A, Moeljono A, Rahmayanti S, Shadrina AN, et al. p63 cytoplasmic aberrance is associated with high prostate cancer stem cell expression. Asian Pac J Cancer Prev 2012;13:1943-8.
8. Oncel S, Cosgul T, Calli A, Calli C, Pinar E. Evaluation of p53, p63, p21, p27, ki-67 in paranasal sinus squamous cell carcinoma and inverted papilloma. Indian J Otolaryngol Head Neck Surg 2011;63:172-7.
9. Kumala S, Septiseptiana EP, Meiyanto EE. Cytotoxic effect of secondary metabolites produced by endophytic fungi 1.3.11, 1.1.6 and 1.2.6 isolated from the fruit of “tanaman Buah Makassar” (Bruce janvanica (L.) merr) on in vitro T47D and MCF7 intact cells and identification of the fungus 1.3.11 by ribosomal DNA sequence analysis. Int J Pharm Pharm Sci 2010;2:80-3.
10. Martin SE, Temm CJ, Goheen MP, Ulbright TM, Hattab EM. Cytoplasmic p63 immunohistochemistry is a useful marker for muscle differentiation: An immunohistochemical and immunoelectron microscopic study. Mod Pathol 2011;24:1320-6.
11. Barbareschi M, Pecciarini L, Cangi MG, Macrì E, Rizzo A, Viale G, et al. p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 2001;25:1054-60.
12. Arslan C, Dizdar O, Altundag K. Pharmacotherapy of triple-negative breast cancer. Expert Opin Pharmacother 2009;10:2081-93.
13. Hicks DG. Immunohistochemistry in the diagnostic evaluation of breast lesions. Appl Immunohistochem Mol Morphol 2011;19:501-5.
14. Won JR, Gao D, Chow C, Cheng J, Lau SY, Ellis MJ, et al. A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard. Mod Pathol 2013;26:1438-50.
15. Zheng Z, Kye Y, Zhang X, Kim A, Kim I. Expression of p63, bcl-2, bcl-6 and p16 in basal cell carcinoma and squamous cell carcinoma of the skin. Korean J Pathol 2005;39:91-8.
16. Yadav R, Sen R, Chauhan P. ER, PR, HER2/NEU status and relation to clinicopathological factors in breast carcinoma. Int J Pharm Pharm Sci 2016;8:287-90.
17. Elsberger B, Lankston L, McMillan DC, Underwood MA, Edwards J. Presence of tumoural C-reactive protein correlates with progressive prostate cancer. Prostate Cancer Prostatic Dis 2011;14:122-8.
18. Tse GM, Tan PH, Chaiwun B, Putti TC, Lui PC, Tsang AK, et al. p63 is useful in the diagnosis of mammary metaplastic carcinomas. Pathology 2006;38:16-20.
19. Alluri P, Newman LA. Basal-like and triple-negative breast cancers: Searching for positives among many negatives. Surg Oncol Clin N Am 2014;23:567-77.
20. Pellegrini G, Dellambra E, Golisano O, Martinelli E, Fantozzi I, Bondanza S, et al. p63 identifies keratinocyte stem cells. Proc Natl Acad Sci U S A 2001;98:3156-61.
21. Yoh KE, Regunath K, Guzman A, Lee SM, Pfister NT, Akanni O, et al. Repression of p63 and induction of EMT by mutant ras in mammary epithelial cells. Proc Natl Acad Sci U S A 2016;113:E6107-16.
22. Hsiao YH, Su YA, Tsai HD, Mason JT, Chou MC, Man YG. Increased invasiveness and aggressiveness in breast epithelia with cytoplasmic p63 expression. Int J Biol Sci 2010;6:428-42.
23. Koker MM, Kleer CG. p63 expression in breast cancer: A highly sensitive and specific marker of metaplastic carcinoma. Am J Surg Pathol 2004;28:1506-12.
24. Dellavalle RP, Walsh P, Marchbank A, Grayson TE, Su LJ, Parker ER, et al. CUSP/p63 expression in basal cell carcinoma. Exp Dermatol 2002;11:203-8.
25. Mathelin C, Annane K, Treisser A, Chenard MP, Tomasetto C, Bellocq JP, et al. Pregnancy and post-partum breast cancer: A prospective study. Anticancer Res 2008;28:2447-52.
26. Hamsagayathri P, Sampath P. Performance analysis of breast cancer classification using decision tree classifiers. Int J Curr Pharm Res 2017;9:19-25.
27. De Laurentiis M, Cianniello D, Caputo R, Stanzione B, Arpino G, Cinieri S, et al. Treatment of triple negative breast cancer (TNBC): Current options and future perspectives. Cancer Treat Rev 2010;36 Suppl 3:S80-6.
28. Kesisis G, Kontovinis LF, Gennatas K, Kortsaris AH. Biological markers in breast cancer prognosis and treatment. J BUON 2010;15:447-54.
29. Dhillon PK, Barry M, Stampfer MJ, Perner S, Fiorentino M, Fornari A, et al. Aberrant cytoplasmic expression of p63 and prostate cancer mortality. Cancer Epidemiol Biomarkers Prev 2009;18:595-600.
30. Narahashi T, Niki T, Wang T, Goto A, Matsubara D, Funata N, et al. Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarcinoma. Histopathology 2006;49:349-57.
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How to Cite
Kamarlis, R., M. Dahlan Lubis, B. Hernowo, A. Kar, and B. Gani. “FREQUENCY AND DISTRIBUTION OF CYTOPLASMIC AND NUCLEAR P63 IN RECOGNIZING THE BASAL-LIKE AND NON-BASAL-LIKE TYPES OF BREAST CANCER BASED ON AGE.”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 1, Jan. 2018, pp. 195-9, doi:10.22159/ajpcr.2018.v11i1.22415.
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