Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Search for accumulation of p53 protein and detection of human papillomavirus genomes in sebaceous gland carcinoma of the eyelid

  • 70 Accesses

  • 39 Citations


Twenty-one Japanese patients with sebaceous carcinoma of the eyelid were investigated for tumour incorporation of human papillomavirus (HPV) types-6, 11, 16, 18, 31, and/or 33 DNA by in situ hybridization with fluorescein isothiocyanate-labelled DNA probes, and for p53 protein accumulation by immunohistochemical analysis with an antibody to p53 protein. Thirteen tumours (61.9%), including 9 cases of multiple infections, were positive for HPV DNA. Positive signal in the nucleus was observed not only in the cancer cells, but also in the cells of surrounding normal sebaceous glands and epidermis. Positive nuclear staining of cancer cells with the antibody to p53 protein was detected in 12 cases (57.1%). p53 protein accumulation was more frequently observed in the clinically advanced cases, occasionally in association with recurrence and/or metastasis. Among the 12 p53-positive cases, 7 were also positive for the presence of HPV DNA. HPV infections exist in a high percentage of sebaceous carcinomas of the eyelid in Japan; the overexpression of p53 protein may be important in both carcinogenesis and progression.

This is a preview of subscription content, log in to check access.


  1. 1.

    Abe M, Ohnishi Y, Hara Y, Shinoda Y, Jingu K (1981) Clinical study of eyelid cancers. Jpn J Clin Ophthalmol 35: 913–919

  2. 2.

    Anwar K, Naiki H, Nakakuki K, Inuzuka M (1992) High frequency of human papillomavirus infection in carcinoma of the urinary bladder. Cancer 70: 1967–1973

  3. 3.

    Bennett WP, Hollstein MC, He A, Zhu SM, Resau JH, Trump BF, Metcalf RA, Welsh JA, Midgley C, Lane DP, Harris CC (1991) Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. Oncogene 6: 1779–1784

  4. 4.

    Boniuk M, Zimmerman LE (1968) Sebaceous carcinoma of the eyelid, eyebrow, caruncle, and orbit. Trans Am Acad Ophthalmol Otolaryngol 72: 619–642

  5. 5.

    Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Pontén J (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA 88: 10124–10128

  6. 6.

    Cooper K, Herrington CS, Evans MF, Gatter KC, McGee JO'D (1993) p53 antigen in cervical condylomata, intraepithelial neoplasia, and carcinoma: relationship to HPV infection and integration. J Pathol 171: 27–34

  7. 7.

    Crook T, Wrede D, Tidy JA, Mason WP, Evans DJ, Vousden KH (1992) Clonal p53 mutation in primary cervical cancer: association with human-papillomavirus-negative tumours. Lancet 339: 1070–1073

  8. 8.

    Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57: 1083–1093

  9. 9.

    Furihata M, Ohtsuki Y, Ogoshi S, Takahashi A, Tamiya T, Ogata T (1993a) Prognostic significance of human papillomavirus genomes (type-16,-18) and aberrant expression of p53 protein in human esophageal cancer. Int J Cancer 54: 226–230

  10. 10.

    Furihata M, Inoue K, Ohtsuki Y, Hashimoto H, Terao N, Fujita Y (1993b) High-risk human papillomavirus infections and overexpression of p53 protein as prognostic indicators in transitional cell carcinoma of the urinary bladder. Cancer Res 53: 4823–4827

  11. 11.

    Graham R, McKee P, McGibbon D, Heyderman E (1985) Torre-Muir syndrome. An association with isolated sebaceous carcinoma. Cancer 55: 2868–2873

  12. 12.

    Hausen H zur (1991) Viruses in human cancers. Science 254: 1167–1173

  13. 13.

    Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253: 49–53

  14. 14.

    Iggo R, Gatter K, Bartek J, Lane D, Harris AL (1990) Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335: 675–679

  15. 15.

    Kass LG, Hornblass A (1989) Sebaceous carcinoma of the ocular adnexa. Surv Ophthalmol 33: 477–490

  16. 16.

    Lassam NJ, From L, Kahn HJ (1993) Overexpression of p53 is a late event in the development of malignant melanoma. Cancer Res 53: 2235–2238

  17. 17.

    Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351: 453–456

  18. 18.

    Lober CW, Fenske NA (1991) Basal cell, squamous cell, and sebaceous gland carcinomas of the periorbital region. J Am Acad Dermatol 25: 685–690

  19. 19.

    Loeffler M, Hornblass A (1990) Characteristics and behavior of eyelid carcinoma (basal cell, squamous cell, sebaceous gland, and malignant melanoma). Ophthalmic Surg 21: 513–518

  20. 20.

    Munroe DG, Peacock JW, Benchimol S (1990) Inactivation of the cellular p53 gene is a common feature of Friend virus-induced erythroleukemia: relationship of inactivation to dominant transforming alleles. Mol Cell Biol 10: 3307–3313

  21. 21.

    Ni C, Kuo PK (1979) Meibomian gland carcinoma. A clinicopathological study of 156 cases with long-period follow-up of 100 cases. Jpn J Ophthalmol 23: 388–401

  22. 22.

    Ni C, Searl SS, Kuo PK, Chu FR, Chong CS, Albert DM (1982) Sebaceous cell carcinomas of the ocular adnexa. Int Ophthalmol Clin 22: 23–61

  23. 23.

    Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342: 705–708

  24. 24.

    Paquette RL, Lee YY, Wilczynski SP, Karmakar A, Kizaki M, Miller CW, Koeffler HP (1993) Mutations of p53 and human papillomavirus infection in cervical carcinoma. Cancer 72: 1272–1280

  25. 25.

    Pérez-Ayala M, Ruiz-Cabello F, Esteban F, Concha A, Redondo M, Oliva MR, Cabrera T, Garrido F (1990) Presence of HPV-16 sequences in laryngeal carcinomas. Int J Cancer 46: 8–11

  26. 26.

    Pfister H (1984) Biology and biochemistry of papillomaviruses. Rev Physiol Biochem Pharmacol 99: 111–181

  27. 27.

    Pfister H (1987) Human papillomaviruses and genital cancer. Adv Cancer Res 48: 113–147

  28. 28.

    Porter PL, Gown AM, Kramp SG, Coltrera MD (1992) Wide-spread p53 overexpression in human malignant tumors. Am J Pathol 140: 145–153

  29. 29.

    Rady P, Scinicariello F, Wagner RF Jr, Tyring SK (1992) p53 mutations in basal cell carcinomas. Cancer Res 52: 3804–3806

  30. 30.

    Rao NA, McLean IW, Zimmerman LE (1978) Sebaceous carcinoma of eyelids and caruncle: correlation of clinicopathologic features with prognosis. In: Jakobiec FA (ed) Ocular and adnexal tumors. Aesculapius, Birmingham, pp 461–476

  31. 31.

    Ro YS, Cooper PN, Lee JA, Quinn AG, Harrison D, Lane D, Horne CHW, Rees JL, Angus B (1993) p53 protein expression in benign and malignant skin tumours. Br J Dermatol 128: 237–241

  32. 32.

    Rodrigues NR, Rowan A, Smith MEF, Kerr IB, Bodmer WF, Cannon JV, Lane DP (1990) p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 87: 7555–7559

  33. 33.

    Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63: 1129–1136

  34. 34.

    Shi SR, Key ME, Kalra KL (1991) Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39: 741–748

  35. 35.

    Tesluk GC (1985) Eyelid lesions: incidence and comparison of benign and malignant lesions. Ann Ophthalmol 17: 704–707

  36. 36.

    Thompson AM, Anderson TJ, Condie A, Prosser J, Chetty U, Carter DC, Evans HJ, Steel CM (1992) p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters. Int J Cancer 50: 528–532

  37. 37.

    Toh Y, Kuwano H, Tanaka S, Baba K, Matsuda H, Sugimachi K, Mori R (1992) Detection of human papillomavirus DNA in esophageal carcinoma in Japan by polymerase chain reaction. Cancer 70: 2234–2238

  38. 38.

    Urano Y, Oura H, Sakaki A, Nagae H, Matsumoto K, Fukuhara K, Nagae T, Arase S, Ninomiya Y, Nakanishi H, Shigemi F, Takeda K (1992) Immunohistological analysis of p53 expression in human skin tumors. J Dermatol Sci 4: 69–75

  39. 39.

    Wynford TD (1992) p53 in tumour pathology: can we trust immunocytochemistry? J Pathol 166: 329–330

  40. 40.

    Yabe H, Kimura C, Hirakata T (1984) Clinico-pathological analysis of patients with primary malignant eyelid tumors. Folia Ophthalmol Jpn 35: 993–997

Download references

Author information

Correspondence to N. Hayashi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hayashi, N., Ueno, H., Furihata, M. et al. Search for accumulation of p53 protein and detection of human papillomavirus genomes in sebaceous gland carcinoma of the eyelid. Vichows Archiv A Pathol Anat 424, 503–509 (1994). https://doi.org/10.1007/BF00191436

Download citation

Key words

  • Human papillomavirus
  • p53 protein Sebaceous gland carcinoma