The presence of HPV 16, 18 and p53 immunohistochemical staining in tumor tissue of Israeli Jewish women with cervical and vulvar neoplasia

The incidence of cervical neoplasia in Israeli Jewish women is persistently lower, while that of vulvar carcinoma is comparable to that in other populations. The aim of the present investigation was to assess the prevalence of HPV and of immunohistochemically detected mutant p53 in Israeli Jewish women with cervical and vulvar neoplasia compared with other populations. Tissue sections from formalin-fixed paraffin-embedded blocks of ten patients with CIN III, 29 with invasive squamous cell carcinoma, three with adenocarcinoma and 14 with invasive vulvar carcinoma, were examined for the presence of HPV 16 and HPV 18 DNA by PCR amplification, and for mutant p53 protein by immunohistochemical staining. HPV negative cases were re-examined with a sensitive primer. HPV DNA was detected in eight patients with CIN III and in 23 patients with invasive squamous carcinoma. In the remaining cervical squamous neoplasia tissue analysis with the sensitive primer could not be done. HPV DNA was also detected in two patients with adenocarcinoma and in nine (64.2%) patients with vulvar carcinoma. Positive p53 immunohistochemical staining was found only in one CIN III patient, in six (20.7%) squamous carcinoma and in 11 (78.6%) vulvar carcinoma patients. Of the p53 immunohistochemical staining positive tissues, two with cervical carcinoma and six with vulvar carcinoma were also HPV-positive. The prevalence of HPV and of positive p53 immunohistochemical staining in our series of Israeli Jewish women with cervical and vulvar neoplasia is similar to that in other populations, suggesting that the etiological factors are probably also alike.

Jewish women; HPV 16, 189; p53; Cervical neoplasia; Vulvar carcinoma

[1] Wemess B. A., Levine A. J., Howley P. M.: "Association of human papilloma virus types 16 and 18 E6 proteins with p53". Science, 1990, 248, 76.

[2] Scheffner M., Munger K., Byrne J. C., Howley P. M.: "The E6 oncoprotein encoded by human papilloma virus types 16 and 18 promotes the degradation of p53". Cell., 1990, 63, 1129.

[3] Bosch F. X., Manos M., Munoz N., Sherman M., Jansen A. M., Peto J., Schiffman M. H. et al.: "Prevalence of human papillomavirus in cervical cancer: a worldwide perspective". J. Natl. Cancer Inst., 1995, 87, 796.

[4] F ujita M., Inoue M., Tanizawa 0., Iwamoto S., Enomoto T.: "Alterations of the p53 gene in human primary cervical carcinoma with and without human papilloma virus infection". Cancer Research, 1992, 52, 5323.

[5] Busby-Earle R. M. C., Steel C. M., Bird C. C.: "Cervical carcinoma: low frequency of allele loss at loci implicated in other common malignancies". Brit. J. Cancer, 1993, 67, 71.

[6] Matsukura M., Sugase M.: "Identification of genital human papillomaviruses in cervical biopsy specimens: segregation of specific virus types in spec巾c clinicopathological lesions". Int. J. Cancer, 1995, 61, 13.

[7] Lorincz A. T., Reid R., Jenson A. B., Greenberg M. D., Lancaster W., Kurman R. J.: "Human papillomavirus infection of the cervix: relative risk association of 15 common anogenital types". Obstet. Gynecol., 1992, 72, 328.

[8] Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J.: "Activating mutations for transformation by p53 produce a gene that forms hsc70 - p53 complex with an altered half life". Mo/. Cell. Biol., 1988, 8, 531.

[9] Kerns B. M., Jordan P. A., Moore M. H., Humphrey P. A., Berchuk A., Kohler M. F., Bast R. C. et al.: "p53 overexpression in formalin-fixed paraffin-embedded tissue detected by immunohistochemistry". 1. Histochem. Cytochem., 1988, 40, 1047.

[10] Kagie M. J., Kenter G. G., Tollennaar R. A., Hermans J., Trimbos J. B., F leuren G. J.: "p53 protein overexpression is common and independent of human papillomavirus infection in squamous cell carcinoma of the vulva". Cancer, 1997, 80, 1228.

[11] Kagie M. J., Kenter G. G., Zommerdijk-Nooijen Y., Hermans J., Schuuring E., Timmers P. J., Trimbos J. B., Fleuren G. J.: "Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin". Gynecol. Oneal., 1997, 67, 178.

[12] Toki T.. Kurman R. J., Park J. S., Kessis T.、Daniel R. W., Shah K. V.: "Probable non-papillomavirus etiology of squamous ceII carcinoma of the vulva in older women. A clinicopathologic study using in situ hybridization and polymerase chain reaction". Int. J. Gynecol. Pathol., 1991, 10, 107.

[13] Pilotti S.. D'Amato L., Della Torre G., Donghi R., Longoni A.. Giarola M.. Sampietro G. et al.: "Papillomavirus, p53 alterations, and primary carcinoma of the vulva". Diagn Mol. Pathol., 1995, 4, 239.

[14] Tervahauta A. I., Syrjanen S. M., Vayrynen M., Saastamoi to the presence of human papillomavirus (HPV) DNA in genital carcinomas and precancer lesions". Anticancer Res., 1993, 13, 1107.

[15] Milde Langosch K., Albrecht K., Joram S., Schlechte H.. Giessing M., Loning T.:''Presence and persistence of HPV infection and p53 in cancer of the cervix uteri and the vulva". Int. J. Cancer, 1995, 36, 639.

[16] Gordinier M. E., Steinhoff M. M., Hogan J. W., Peipert J F., Gajewski W. H., Falkenberry S. S., Granai C. O.: "Sphase fraction. p53, and HER-2/neu statuS as predictors of nodal metastaSIs in early vulvar cancer". Gynecol. Oncol., 1997, 67, 200.

[17] McConnell D. T., Miller I. D., Parkin D. E., Murray G. I.: "p53 protein expression in a population-based series of primary vulvaL squamous cell carcinoma and immediate adjacent field change". Gvnecol. Oneal. 1997, 67, 248.

[18] Barchana M., Andreev H., Alon R.: "I srael Cancer Registry". Cancer in Israel 1994 Ministry of Health. Jerusalem 1997.

[19] Marcus S. L.: "Multiple squamous cell carcinoma involving the cervix, vagina, and vulva. The theory of multicentric origin". Am. J. Obstet. Gynecol., 1960, 80, 802.

[20] Rutledge F., Smith J.P., Franklin E.W.: "Carcinoma of the vulva". Am. J. Obstet. Gynecol., 1970, 106, 1117.

[21] Jimerson G. K., Merill J. A.: "Multicentric squamous malignancy involving both cervix and vulva". Cancer, 1970, 26, 150.

[22] Franklin E.W., Rutledge F. D.: "Epidemiology of epidermoid carcinoma of the vulva". Obstet. Gynecol., 1970, 39, 165.

[23] Menczer J., Voliovitch Y., Modan B.. Modan M., Steinitz R.: "Some epidemiologic aspects of carcinoma of the vulva in Israel". Am. J. Obstet. Gynecol., 1982, 143, 893.

[24] Sherman L., Malloul N.. Golan I., Durst M., Baram A.: "Expression and splicing patterns of human papillomavirus type-16 mRN As in pre-cancerous lesions and carcinomas of the cervix in human keratinocytes immortalized by HP V 16, and in cell lines established from cervical cancers". Int. J. Cancer, 1992, 50, 356.

[25] Mitrani-Rosenbaum S.. Gal D., F riedman M., Kitron N., Tsviel R., Mordel N., Anteby S. O.: "Papillomaviruses in lesions of the lower genital tract in Israeli patients". Eur. J. Cancer Clin. Oncol., 1988, 24, 725.

[26] Uchiyama M., Iwasaka T., Matsuo N., Hachisugo T., Mon M., Sugimori H.: "Correlation between human papilloma virus and p53 gene overexpression in adenocarcinoma of the uterine cervix". Gynecol. Oncol., 1997, 65, 23.

[27] Parker M. F.,A miyo G. F.,G eradts J.,S bichi A. L., Park R C., Taylor R. R., Birrer M. J.: "Molecular characterization of adenocarcinoma of the cervix". Gynecol. Oneal., 1997, 64, 242.

[28] Isacsohn M., Dolberg L., Gottschalk Sabag S., MitraniRosenbaum S., Nubani N., Diamant Y. Z., Goldsmidt R.: "The inter-relationship of herpes virus, papilloma 16/18 virus infection and pap smear pathology in Israeli women" Isr. J. Med. Sci, 1994, 30, 383.

[29] Menczer J., Leventon-Kriss S., Modan M., Oelsner G .. Gerichter C. B.: "Antibodies to herpes simplex virus in Jewish women with cervical cancer and in healthy Jewish women of Israel". J. Natl. Cancer Inst., 1975, 55, 3.

[30] Baram A., Schachter A.: "Cervical carcinoma: disease of the future for Jewish women". Lancet, 1982, i, 747.

[31] Glezerman M., Piura B., Insler V.:''Cervical cancer In Jewish women".Am. J. Obstet. Gynecol., 1989, 161, 1186.

[32) Hording U.. Junge J.. Daugaard S., Lundvall F.. Poulsen H., Bock J. E.: "Yulvar squamous cell carcinoma and papillomaviruses: indication for two different etiologies". Gynecol. Oncol., 1994, 52, 241.

[33] Nuovo G. J., Delvenne P., Macconnell P., Chalas E., Neto C., Mann W. J.: "Correlation of histology and detection of human papillomavirus DNA in vulvar cancer". Gynecol. Oneal., 1991,43, 275.

[34] Monk B. J., Burger R. A.. Lin F.. Parham G., Yasilev S. A., Wilczynski S. P.:''Prognostic significanee of human papillomavirus DNA in vulvar carcinoma''. Obstet. Gynecol.. 1995, 85, 709.

[35] Iwasawa A., Nieminen P.. Lehtinen M., P aavonen J.: "Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain reaction". Obstet. Gynecol., 1997, 89, 81.

[36] Bosari S., Roncalli M., Yiale G., Bossi P., Cogisi G:: "p53 immunoreactivity in inflammatory and neoplastic diseases of the uterine cervix". J. Pathol., 1993, 169, 425.

[37] Oka K., Nakano T., Arai T.: "p53CMI expre沁ion is not associated with prognosis in uterine cervical carcinoma". Cancer, 1993, 72, 160.

[38] Gitsch G., Kainz C.、Joura E., Breitenecker G.: "Mutant p53 product in patients with stage III cervical cancer". Anticancer Res., 1992, 12, 2241.

[39] Kainz C., Kohlberger P., Gitsch G., Sliutz G.. Breitenecker G., Reinthaller A.: "Mutant p53 in patients with invasive cervical cancer stages IB to IIB". Gynecol. Oneal., 1995, 57, 212.

[40] Holm R., Skomedal H., Helland P., Borresen A., Nesland J. M.: "Immunohis tochemical analysis of p53 protein overexpression in normal, premalignant and malignant tissues of the cervix". J. Pathol., 1995, 169, 21.

[41] Mital K. R., Lin 0., Chan W., Goswami S., Demopoulus R I.: "Cervical squamous dysplasias and carcinomas with immunodetectable p53 frequently contain HPV". Gynecol Oncol., 1995, 58, 289.

[42] Schneider J., Rubio M. P., Rodriguez-Escudero F. J., Se, zinger B. R., Castresane J. S.: "Identification of p53 mutations by means of single strand conformation polymorphism analysis in gynaecological tumors: comparison with results of immunohistochemistry". Eu,: J. Cancer, 1994, 30A, 504.

[43] MacGeoch C., Barnes D. M., Newton J. A., Mohamed S., Hodgson S. Y., Ng M., Bishop D. T., Spurr N. K.: p53 protein detected by immunohistochemical staining is not always mutant". Dis. Markers, 1993, 11, 239.

[44] Hietanen S. H., Kurvinen K., Syrjanen K., Grenman S., Carey T., McClatchey K., Syrjanen S.: "Mutation of tumor suppressor gene p53 is frequently found in vulvar carcinoma cells". Am. J. Obstet. Gynecol., 1995. 173, 1477.

[45] Sliutz G.、Schmidt W., Tempfer C., Speiser P., Gitsch G., Eder S. et al.: "Detection of p53 point mutations in primary human vu Ivar cancer by PCR and temperature gradient gel electrophoresis". Gynecol. Oncol., 1997, 64. 93,

[46] Pilotti S., Donghi R., D'Amato L. et al.: "Papillomavirus, p53 alteration and primary carcinoma of the vulva". Eur. J. Cancer, 1993, 29A, 924.

[47] Schiffman M. H.: "Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia". J. Natl. Cancer Inst., 1992, 84, 394.

[48] Lee Y. Y., Wilczynski S. P., Chumakov A., Chih D., Koeffler H. P.: "Carcinoma of the vulva: HPV and p53 mutations". Oncogene, 1994, 9, 1655.

[49] Menczer J., Barchana M., Andreev H., Arbel-Alo n S., Modan B.: "Selected epidemiological time trends of vulvar carcinoma in Israel". Int. J. Gynecol. Cancer, 1999, 9, 24.