Advertisement
Research Article| Volume 15, ISSUE 3, P727-742, September 1995

Immunohistochemical Approaches to Diagnosis in Gynecologic Pathology

  • Jay H. Beckstead
    Correspondence
    Address reprint requests to Jay H. Beckstead, MD Department of Pathology, LI 13 Oregon Health Sciences University 3181 SW Sam Jackson Park Road Portland, OR 97201
    Affiliations
    From the Department of Pathology, Oregon Health Sciences University, Portland, Oregon
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      Immunohistochemical techniques have become widely used in gynecologic pathology in recent years. This article is divided into sections of major anatomic areas of gynecologic interest, and each section discusses specific pathologic questions approachable by these studies. A description of reagents, as they apply in each case, is also included.
      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'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ambros R.A.
        • Park J.S.
        • Shah K.V.
        • et al.
        Evaluation of histologic, morphometric, and immunohistochemical criteria in the differential diagnosis of small cell carcinomas of the cervix with particular reference to human papillomavirus types 16 and 18 [published erratum appears in Mod Pathol 5:40, 1992].
        Mod Pathol. 1991; 4: 586-593
        • Auerbach H.E.
        • LiVolsi V.A.
        • Merino M.J.
        Malignant mixed mullerian tumors of the uterus. An immunohistochemical study.
        Int J Gynecol Pathol. 1988; 7: 123-130
        • Azumi N.
        • Ben-Ezra J.
        • Battifora H.
        Immunophenotypic diagnosis of leiomyosarcomas and rhabdomyosarcomas with monoclonal antibodies to muscle-specific actin and desmin in formalin-fixed tissue.
        Mod Pathol. 1988; 1: 469-474
        • Bonazzi del Poggetto C.
        • Virtanen I.
        • Lehto V.P.
        • et al.
        Expression of intermediate filaments in ovarian and uterine tumors.
        Int J Gynecol Pathol. 1983; 1: 359-366
        • Borazjani G.
        • Twiggs L.B.
        • Leung B.S.
        • et al.
        Prognostic significance of steroid receptors measured in primary metastatic and recurrent endometrial carcinoma.
        Am J Obstet Gynecol. 1989; 161: 1253-1257
        • Brescia R.J.
        • Kurman R.J.
        • Main C.S.
        • et al.
        Immunocytochemical localization of chorionic gonadotropin, placental lactogen, and placental alkaline phosphatase in the diagnosis of complete and partial hydatidiform moles.
        Int J Gynecol Pathol. 1987; 6: 213-229
        • Brisigotti M.
        • Moreno A.
        • Murcia C.
        • et al.
        Verrucous carcinoma of the vulva. A clinicopathologic and immunohistochemical study of five cases.
        Int J Gynecol Pathol. 1989; 8: 1-7
        • Brown D.C.
        • Theaker J.M.
        • Banks P.M.
        • et al.
        Cytokeratin expression in smooth muscle and smooth muscle tumors.
        Histopathol. 1987; 11: 477-486
        • Carcangiu M.I.
        • Chambers J.T.
        • Voynick I.M.
        • et al.
        Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part I: Clinical and histologic correlations.
        Am J Clin Pathol. 1990; 94: 247-254
        • Chambers J.T.
        • Carcangiu M.L.
        • Voynick I.M.
        • et al.
        Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part II: Correlation between biochemical and immunohistochemical methods and survival.
        Am J Clin Pathol. 1990; 94: 255-260
        • Cintorino M.
        • Bellizzi de Marco E.
        • Leoncini P.
        • et al.
        Expression of alpha-smooth-muscle actin in stromal cells of the uterine cervix during epithelial neoplastic changes.
        Int J Cancer. 1991; 47: 843-846
        • Costa M.J.
        • DeRose P.B.
        • Roth L.M.
        • et al.
        Immunohistochemical phenotype of ovarian granulosa cell tumors: Absence of epithelial membrane antigen has diagnostic value.
        Hum Pathol. 1994; 25: 60-66
        • Czernobilsky B.
        • Moll R.
        • Franke W.W.
        • et al.
        Intermediate filaments of normal and neoplastic tissues of the female genital tract with emphasis on problems of differential tumor diagnosis.
        Pathol Res Pract. 1984; 179: 31-57
        • Czernobilsky B.
        • Shezen E.
        • Lifschitz-Mercer B.
        • et al.
        Alpha smooth muscle actin (alpha-SM actin) in normal human ovaries, in ovarian stromal hyperplasia and in ovarian neoplasms.
        Virchows Arch B Cell Pathol. 1989; 57: 55-61
        • Dabbs D.J.
        • Geisinger K.R.
        • Norris H.T.
        Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns.
        Am J Surg Pathol. 1986; 10: 568-576
        • Dallenbach-Hellweg G.
        • Lang G.
        Immunohistochemical studies on uterine tumors. I. Invasive squamous cell carcinomas of the cervix and their precursors.
        Pathol Res Pract. 1991; 187: 36-43
        • Darne J.
        • Soutter W.P.
        • Ginsberg R.
        • et al.
        Nuclear and “cytoplasmic” estrogen and progesterone receptors in squamous cell carcinoma of the cervix.
        Gynecol Oncol. 1990; 38: 216-219
        • Davies J.O.
        • Davies E.R.
        • Howe K.
        • et al.
        Practical application of monoclonal antibody (NDOG2) against placental alkaline phosphatase in ovarian cancer.
        J Roy Soc Med. 1985; 78: 899-905
        • Deamant F.D.
        • Pombo M.T.
        • Battifora H.
        Estrogen receptor immunohistochemistry as a predictor of site of origin in metastatic breast cancer.
        Appl Immunohistochem. 1993; 1: 188-192
        • Ehrmann R.L.
        • Dwyer I.M.
        • Yavner D.
        • et al.
        An immunohistochemical study of laminin and type IV collagen distribution in carcinoma of the cervix and vulva.
        Obstet Gynecol. 1988; 72: 257-262
        • Esquius J.
        • Brisigotti M.
        • Matias-Guiu X.
        • et al.
        Keratin expression in normal vulva, non-neoplastic epithelial disorders, vulvar intraepithelial neoplasia, and invasive squamous cell carcinoma.
        Int J Gynecol Pathol. 1991; 10: 341-355
        • Farhood A.I.
        • Abrams J.
        Immunohistochemistry of endometrial stromal sarcoma.
        Hum Pathol. 1991; 22: 224-230
        • Fleuren G.J.
        • Nap M.
        Carcinoembryonic antigen in primary and metastatic ovarian tumors.
        Gynecol Oncol. 1988; 30: 407-415
        • Fowler L.J.
        • Maygarden S.J.
        • Novotny D.B.
        Human alveolar macrophage-56 and carcinoembryonic antigen monoclonal antibodies in the differential diagnosis between primary ovarian and metastatic gastrointestinal carcinomas.
        Hum Pathol. 1994; 25: 666-670
        • Franquemont D.W.
        • Frierson Jr, H.F.
        • Mills S.E.
        An immunohistochemical study of normal endometrial stroma and endometrial stromal neoplasms. Evidence for smooth muscle differentiation.
        Am J Surg Pathol. 1991; 15: 861-870
        • Geisinger K.R.
        • Marshall R.B.
        • Kute T.E.
        • et al.
        Correlation of female sex steroid hormone receptors with histologic and ultrastructural differentiation in adenocarcinoma of the endometrium.
        Cancer. 1986; 58: 1506-1517
        • Gigi-Leitner O.
        • Geiger B.
        • Levy R.
        • et al.
        Cytokeratin expression in squamous metaplasia of the human uterine cervix.
        Differentiation. 1986; 31: 191-205
        • Gown A.M.
        • Boyd H.C.
        • Chang Y.
        • et al.
        Smooth muscle cells can express cytokeratins of “simple” epithelium. Immunocytochemical and biochemical studies in vitro and in vivo.
        Am J Pathol. 1988; 132: 223-232
        • Hammond R.H.
        • Bates T.D.
        • Clarke D.G.
        • et al.
        The immunoperoxidase localization of tumour markers in ovarian cancer: the value of CEA, EMA, cytokeratin and DD9.
        Br J Obstet Gynaecol. 1991; 98: 73-83
        • Harms D.
        • Janig U.
        Germ cell tumors of childhood. Report of 170 cases including 59 pure and partial yolk-sac tumours.
        Virchows Arch A Pathol Anat Histopathol. 1986; 409: 223-239
        • Ishikura H.
        • Scully R.E.
        Hepatoid carcinoma of the ovary. A newly described tumor.
        Cancer. 1987; 60: 2775-2784
        • Ivanyi D.
        • Ansink A.
        • Groeneveld E.
        • et al.
        New monoclonal antibodies recognizing epidermal differentiation-associated keratins in formalin-fixed, paraffin-embedded tissue. Keratin 10 expression in carcinoma of the vulva.
        J Pathol. 1989; 159: 7-12
        • Ivanyi D.
        • Groeneveld E.
        • Van Doomewaard G.
        • et al.
        Keratin subtypes in carcinomas of the uterine cervix: Implications for histogenesis and differential diagnosis.
        Cancer Res. 1990; 50: 5143-5152
        • Khalifa M.A.
        • Sesterhenn I.A.
        Tumor markers of epithelial ovarian neoplasms.
        Int J Gynecol Pathol. 1990; 9: 217-230
        • Khong T.Y.
        • Lane E.B.
        • Robertson W.B.
        An immunocytochemical study of fetal cells at the maternal-placental interface using monoclonal antibodies to keratins, vimentin and desmin.
        Cell Tissue Res. 1986; 246: 189-195
        • Kleine W.
        • Maier T.
        • Geyer H.
        • et al.
        Estrogen and progesterone receptors in endometrial cancer and their prognostic relevance.
        Gynecol Oncol. 1990; 38: 59-65
        • Konishi I.
        • Fujii S.
        • Kataoka N.
        • et al.
        Ovarian mucinous cystadenocarcinoma producing alpha-fetoprotein.
        Int J Gynecol Pathol. 1988; 7: 182-189
        • Konishi I.
        • Fujii S.
        • Nonogaki H.
        • et al.
        Immunohistochemical analysis of estrogen receptors, progesterone receptors, Ki-67 antigen, and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix.
        Cancer. 1991; 68: 1340-1350
        • Kurman R.J.
        • Young R.H.
        • Norris H.J.
        • et al.
        Immunocytochemical localization of placental lactogen and chorionic gonadotropin in the normal placenta and trophoblastic tumors, with emphasis on intermediate trophoblast and the placental site trophoblastic tumor.
        International Journal of Gynecol Pathol. 1984; 3: 101-121
        • Lifschitz-Mercer B.
        • Czernobilsky B.
        • Dgani R.
        • et al.
        Immunocytochemical study of an endometrial diffuse clear cell stromal sarcoma and other endometrial stromal sarcomas.
        Cancer. 1987; 59: 1494-1499
        • Lifschitz-Mercer B.
        • Czernobilsky B.
        • Shezen E.
        • et al.
        Selective expression of cytokeratin polypeptides in various epithelia of human Brenner tumor.
        Hum Pathol. 1988; 19: 640-650
        • Lin M.
        • Hanai J.
        • Wada A.
        • et al.
        S-100 protein in ovarian tumors. A comparative immunohistochemical study of 135 cases.
        Acta Pathol Jpn. 1991; 41: 233-239
        • Lindgren J.
        • Vesterinen E.
        • Purola E.
        • et al.
        Prognostic significance of tissue carcinoembryonic antigen in mild dysplasia of the uterine cervix.
        Tumor Biol. 1986; 6: 465-470
        • Martin J.D.
        • Hahnei R.
        • McCartney A.J.
        • et al.
        The influence of estrogen and progesterone receptors on survival in patients with carcinoma of the uterine cervix.
        Gynecol Oncol. 1986; 23: 329-335
        • Matsukuma K.
        • Tsukamoto N.
        Alpha-fetoprotein producing endometrial adenocarcinoma.
        Gynecol Oncol. 1988; 29: 370-377
        • McDicken I.W.
        • Rainey M.
        The immunohistological demonstration of carcinoembryonic antigen in intra-epithelial and invasive squamous carcinoma of the cervix.
        Histopathol. 1983; 7: 475-485
        • McLaughlin P.J.
        • Warne P.H.
        • Hutchinson G.E.
        • et al.
        Placental-type alkaline phosphatase in cervical neoplasia.
        Br J Cancer. 1987; 55: 197-201
        • McNutt M.A.
        • Bolen J.W.
        • Gown A.M.
        • et al.
        Coexpression of intermediate filaments in human epithelial neoplasms.
        Ultrastruct Pathol. 1985; 9: 31-43
        • Miettinen M.
        • Franssila K.
        Immunohistochemical spectrum of malignant melanoma. The common presence of keratins.
        Lab Invest. 1989; 61: 623-628
        • Miettinen M.
        • Lehto V.P.
        • Virtanen I.
        Expression of intermediate filaments in normal ovaries and ovarian epithelial, sex cord-stromal, and germinal tumors.
        Int J Gynecol Pathol. 1983; 2: 64-71
        • Miettinen M.
        • Wahlstrom T.
        • Virtanen I.
        • et al.
        Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied with antibodies to intermediate-filament proteins.
        Am J Surg Pathol. 1985; 9: 640-651
        • Moll I.
        • Moll R.
        Cells of extramammary Paget’s disease express cytokeratins different from those of epidermal cells.
        J Invest Dermatol. 1985; 84: 3-8
        • Moll R.
        • Franke W.W.
        • Schiller D.L.
        • et al.
        The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors, and cultured cells.
        Cell. 1982; 31: 11-24
        • Moll R.
        • Levy R.
        • Czernobilsky B.
        • et al.
        Cytokeratins of normal epithelia and some neoplasms of the female genital tract.
        Lab Invest. 1983; 49: 599-610
        • Moll R.
        • Lowe A.
        • Laufer J.
        • et al.
        Cytokeratin 20 in human carcinomas. A new histodiag-nostic marker detected by monoclonal antibodies.
        Am J Pathol. 1992; 140: 427-447
        • Moll R.
        • Pitz S.
        • Levy R.
        • et al.
        Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas.
        Hum Pathol. 1991; 22: 989-1001
        • Mosny D.S.
        • Herholz J.
        • Degen W.
        • et al.
        Immunohistochemical investigations of steroid receptors in normal and neoplastic squamous epithelium of the uterine cervix.
        Gynecol Oncol. 1989; 35: 373-377
        • Nagle R.B.
        • Clark V.A.
        • McDaniel K.M.
        • et al.
        Immunohistochemical demonstration of keratins in human ovarian neoplasms. A comparative method.
        J Histochem Cytochem. 1983; 31: 1010-1014
        • Nagle R.B.
        • Lucas D.O.
        • McDaniel K.M.
        • et al.
        New evidence linking mammary and extramammary Paget cells to a common cell phenotype.
        Am J Clin Pathol. 1985; 83: 431-438
        • Navarro D.
        • Cabrera J.J.
        • Leon L.
        • et al.
        Endometrial stromal sarcoma expression of estrogen receptors, progesterone receptors and estrogen-induced srp27 (24K) suggests hormone responsiveness.
        J Steroid Biochem Mol Biol. 1992; 41: 589-596
        • Neunteufel W.
        • Breitenecker G.
        CA 19-9, CA 125 and CEA in the endometrial mucosa during the menstrual cycle, in atypical hyperplasia and endometrial carcinoma.
        Cancer Lett. 1989; 48: 77-83
        • Norton A.J.
        • Thomas J.A.
        • Isaacson P.G.
        Cytokeratin-specific monoclonal antibodies are reactive with tumours of smooth muscle derivation. An immunocytochemical and biochemical study using antibodies to intermediate filament cytoskeletal proteins.
        Histopathol. 1987; 11: 487-499
        • Puts J.
        • Moesker O.
        • Aldeweireldt J.
        • et al.
        Application of antibodies to intermediate filament proteins in simple and complex tumors of the female genital tract.
        Int J Gynecol Pathol. 1987; 6: 257-274
        • Raju G.C.
        Expression of the cytokeratin marker CAM 5.2 in cervical neoplasia.
        Histopathol. 1988; 12: 437-443
        • Ramaekers F.
        • van Niekerk C.
        • Poels L.
        • et al.
        Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas.
        Am J Pathol. 1990; 136: 641-655
        • Ramaekers F.C.
        • Puts J.J.
        • Kenemans P.
        • et al.
        Use of intermediate filament antibodies in the differential diagnosis of gynecological neoplasia.
        Eur J Obstet Gynecol Reprod Biol. 1985; 19: 347-353
        • Ramaekers F.C.
        • Verheijen R.H.
        • Moesker O.
        • et al.
        Mesodermal mixed tumor. Diagnosis by analysis of intermediate filament proteins.
        Am J Surg Pathol. 1983; 7: 381-385
        • Runowicz C.D.
        • Nuchtern L.M.
        • Braunstein J.D.
        • et al.
        Heterogeneity in hormone receptor status in primary and metastatic endometrial cancer.
        Gynecol Oncol. 1990; 38: 437-441
        • Scambia G.
        • Panici P.B.
        • Baiocchi G.
        • et al.
        Steroid hormone receptors in carcinoma of the cervix: Lack of response to an antiestrogen.
        Gynecol Oncol. 1990; 37: 323-326
        • Smedts F.
        • Ramaekers F.
        • Robben H.
        • et al.
        Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia.
        Am J Pathol. 1990; 136: 657-668
        • Smedts F.
        • Ramaekers F.
        • Troyanovsky S.
        • et al.
        Keratin expression in cervical cancer.
        Am J Pathol. 1992; 141: 497-511
        • Smedts F.
        • Ramaekers F.
        • Troyanovsky S.
        • et al.
        Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia.
        Am J Pathol. 1992; 140: 601-612
        • Szpak C.A.
        • Soper J.T.
        • Thor A.
        • et al.
        Detection of adenocarcinoma in peritoneal washings by staining with monoclonal antibody B72.3.
        Acta Cytol. 1989; 33: 205-214
        • Thor A.
        • Viglione M.J.
        • Muraro R.
        • et al.
        Monoclonal antibody B72.3 reactivity with human endometrium: A study of normal and malignant tissues.
        Int J Gynecol Pathol. 1987; 6: 235-247
        • Tosi P.
        • Sforza V.
        • Santopietro R.
        Estrogen receptor content, immunohistochemically determined by monoclonal antibodies, in endometrial stromal sarcoma.
        Obstet Gynecol. 1989; 73: 75-78
        • Ueda G.
        • Yamasaki M.
        Neuroendocrine carcinoma of the uterus.
        Curr Topics Pathol. 1992; 85: 309-335
        • van Niekerk C.C.
        • Ramaekers F.C.
        • Hanselaar A.G.
        • et al.
        Changes in expression of differentiation markers between normal ovarian cells and derived tumors.
        Am J Pathol. 1993; 142: 157-177
        • Viale G.
        • Gambacorta M.
        • DelTOrto P.
        • et al.
        Coexpression of cytokeratins and vimentin in common epithelial tumors of the ovary: An immunocytochemical study of eighty-three cases.
        Virchows Arch A Pathol Anatomy Histopathol. 1988; 413: 91-101
        • Younes M.
        • Katikaneni P.
        • Lechago L.
        • et al.
        HAM56 antibody: A tool in the differential diagnosis between colorectal and gynecological malignancy.
        Mod Pathol. 1994; 7: 396-400
        • Zirker T.A.
        • Silva E.G.
        • Morris M.
        • et al.
        Immunohistochemical differentiation of clear-cell carcinoma of the female genital tract and endodermal sinus tumor with the use of alpha-fetoprotein and Leu-Ml.
        Am J Clin Pathol. 1989; 91: 511-514