The differential expression of the HER-2/neu oncogene among high-risk human papillomavirus–infected glandular lesions of the uterine cervix


      OBJECTIVE: Our purpose was to examine the relationship between HER-2/neu expression and human papillomavirus infection in cervical glandular neoplasia. STUDY DESIGN: Cases of cervical adenocarcinoma in situ and invasive adenocarcinoma were selected for study. Human papillomavirus typing was performed by in situ hybridization. HER-2/neu was detected by in situ hybridization and immunohistochemistry. Fisher's exact test was used to assess for statistical significance. RESULTS: Fifteen cases of adenocarcinoma in situ and invasive adenocarcinoma were analyzed. In situ hybridization detected HER-2/neu messenger ribonucleic acid in 8 cases, whereas immunohistochemistry detected protein in 5 cases. Overall, HER-2/neu activity was present in 10 cases (66.7%). HER-2/neu messenger ribonucleic acid was detected more commonly in lesions associated with human papillomavirus type 16 versus type 18 (85.7% vs 25.0%, p = 0.04). CONCLUSION: HER-2/neu is frequently expressed in human papillomavirus–infected glandular lesions of the cervix. In situ hybridization may provide a more sensitive indicator of HER-2/neu activity over immunohistochemistry. Preferential expression of HER-2/neu messenger ribonucleic acid was detected in human papillomavirus type 16 versus type 18 lesions. Further study is warranted to examine relationships between human papillomavirus infection and HER-2/neu expression. (Am J Obstet Gynecol 1997;177:133-8)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Schechter AL
        • Stern DF
        • Vaidyanathan L
        • Decker SJ
        • Drebin JA
        • Greene MI
        • et al.
        The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen.
        Nature. 1984; 312: 513-516
        • Bargmann CI
        • Hung MC
        • Weinberg RA.
        The neu oncogene encodes an epidermal growth factor receptor–related protein.
        Nature. 1986; 319: 226-230
        • Yamamoto T
        • Ikava S
        • Akiyama T
        • Semba K
        • Nomura N
        • Miyajima N
        • et al.
        Similarity of protein encoded by the c-erbB-2 gene to epidermal growth factor receptor.
        Nature. 1986; 319: 230-234
        • Hung M
        • Matin A
        • Zhang Y
        • Xing X
        • Sorgi F
        • Huang L
        • et al.
        HER-2/neu-targeting gene therapy—a review.
        Gene. 1995; 159: 65-71
        • Akiyama T
        • Saito T
        • Ogawara H
        • Toyoshima K
        • Yamamoto T.
        Tumor promoter and epidermal growth factor stimulate phosphorylation of the c-erbB-2 gene product in MKN-7 human adenocarcinoma cells.
        Mol Cell Biol. 1988; 8: 1019-1026
        • Graus-Porta D
        • Beerli RR
        • Hynes NE.
        Single-chain antibody-mediated intracellular retention of erbB-2 impairs neu differentiation factor and epidermal growth factor signaling.
        Mol Cell Biol. 1995; 15: 1182-1191
        • Bargmann C
        • Hung M
        • Weinberg R.
        Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185.
        Cell. 1986; 45: 649-657
        • Slamon DJ
        • Godolphin W
        • Jones LA
        • Holt JA
        • Wong SG
        • Keith DE
        • et al.
        Studies of HER-2/neu proto-oncogene in human breast and ovarian cancer.
        Science. 1989; 244: 707-712
        • Hale RJ
        • Buckley CH
        • Fox H
        • Williams J.
        Prognostic value of c-erbB-2 expression in uterine cervical carcinoma.
        J  Clin Pathol. 1992; 45: 594-596
        • Brumm C
        • Riviere A
        • Wilckens C
        • Loning T.
        Immunohistochemical investigation and Northern blot analysis of c-erbB-2 expression in normal, premalignant and malignant tissues of the corpus and cervix uteri.
        Virchows Arch. 1990; 417: 477-484
        • Kihana T
        • Tsuda H
        • Teshima S
        • Nomoto K
        • Tsugane S
        • Sonoda T
        • et al.
        Prognostic significance of the overexpression of c-erbB-2 protein in adenocarcinoma of the uterine cervix.
        Cancer. 1994; 73: 148-153
        • Mandai M
        • Konishi I
        • Koshiyama M
        • Komatsu T
        • Yamamoto S
        • Nanbu K
        • et al.
        Altered expression of nm23-H1 and c-erbB-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix.
        Cancer. 1995; 75: 2523-2529
        • Costa MJ
        • Walls J
        • Trelford JD.
        c-erbB-2 oncoprotein overexpression in uterine cervix carcinoma with glandular differentiation.
        Am J Clin Pathol. 1995; 104: 634-642
        • Berchuck A
        • Rodriguez G
        • Kamel A
        • Soper JT
        • Clarke-Pearson DL
        • Bast RC.
        Expression of epidermal growth factor receptor and HER-2/neu in normal and neoplastic cervix, vulva, and vagina.
        Obstet Gynecol. 1990; 76: 381-387
        • zur Hausen H
        • de Villiers EM
        Human papillomaviruses.
        Annu Rev Microbiol. 1994; 48: 427-447
      1. Chow LT, Broker TR. Small DNA tumor viruses. In: Nathanson N, editor. Viral pathogenesis. Philadelphia: Lippincott-Raven Press. In press.

        • Tervahauta A
        • Syrjanen S
        • Syrjanen K.
        Epidermal growth factor receptor, c-erbB-2 proto-oncogene and estrogen receptor expression in human papillomavirus lesions of the uterine cervix.
        Int J Gynaecol Obstet. 1994; 13: 234-240
        • Stoler MH.
        The biology of human papillomaviruses and their role in cervical carcinogenesis.
        in: Cytopathology of the female genital tract. Lippincott, Philadelphia1996: 51-72
        • Stoler M
        • Broker T.
        In situ hybridization detection of human papillomavirus DNA and messenger RNA in genital condylomas and a cervical carcinoma.
        Hum Pathol. 1986; 17: 1250-1258
        • Angerer LM
        • Stoler MS
        • Angerer RC.
        situ hybridization with RNA probes: an annotated recipe.
        in: In situ hybridization: applications to neurobiology. Oxford University Press, Oxford (NY)1987: 42-70
        • Stoler MH
        • Rhodes CR
        • Whitbeck A
        • Wolinsky SM
        • Chow LT
        • Broker TR.
        Human papillomavirus type 16 and 18 gene expression in cervical neoplasia.
        Hum Pathol. 1992; 23: 117-128
        • Stoppler H
        • Stoppler MC
        • Schlegel R.
        Transforming proteins of the papillomaviruses.
        Intervirology. 1994; 37: 168-179
        • Yan DH
        • Chang LS
        • Hung MC.
        Repressed expression of the HER-2/c-erbB-2 proto-oncogene by the adenovirus Ela gene products.
        Oncogene. 1991; 6: 343-345
        • Matin A
        • Hung MC.
        Negative regulation of the neu promoter by the SV40 large T antigen.
        Cell Growth Differ. 1993; 4: 1051-1056
        • Zyzak LL
        • MacDonald LM
        • Batova A
        • Forand R
        • Creek KE
        • Pirisi L.
        Increased levels and constitutive tyrosine phosphorylation of the epidermal growth factor receptor contribute to autonomous growth of human papillomavirus type 16 immortalized human keratinocytes.
        Cell Growth Differ. 1994; 5: 537-547