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. 1998 Oct;78(8):1091–1094. doi: 10.1038/bjc.1998.633

CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer.

C Tempfer 1, G Sliutz 1, G Haeusler 1, P Speiser 1, A Reinthaller 1, G Breitenecker 1, N Vavra 1, C Kainz 1
PMCID: PMC2063157  PMID: 9792156

Abstract

Expression of alternatively spliced CD44 isoforms has been reported to correlate with poor prognosis in human squamous cell cancers, i.e. squamous cell cancer of the lung and cervix. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage squamous cell cancer of the vulva. Seventy cases of squamous cell carcinoma of the vulva International Federation of Gynaecology and Obstetrics (FIGO) stage I were examined immunohistochemically for expression of CD44 isoforms. We used four different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v3, v5, v6 and v7-8 of human variant CD44. The correlation of CD44 expression with histological grade and disease-free and overall survival was investigated. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 28% (20/70), 47% (33/70), 33% (23/70) and 17% (12/70) of the tumour samples respectively. Patients suffering from tumours expressing CD44v6 had a poorer relapse-free (log-rank test, P = 0.02) and overall survival (log-rank test, P = 0.03). Likewise, patients suffering from tumours expressing CD44v3 had a poorer relapse-free (log-rank test, P = 0.04) and overall survival (log-rank test, P = 0.01). Expression of CD44v5 and CD44v7-8 did not compromise the patients' outcome. Histological grade did not correlate with CD44 isoform expression. Immunohistochemically detected expression of CD44 isoforms containing variant exon v6 or v3 is correlated with a poor relapse-free and overall survival in FIGO stage I vulvar cancer patients.

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Selected References

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  1. Ambros R. A., Kallakury B. V., Malfetano J. H., Mihm M. C., Jr Cytokine, cell adhesion receptor, and tumor suppressor gene expression in vulvar squamous carcinoma: correlation with prominent fibromyxoid stromal response. Int J Gynecol Pathol. 1996 Oct;15(4):320–325. doi: 10.1097/00004347-199610000-00004. [DOI] [PubMed] [Google Scholar]
  2. Cannistra S. A., Abu-Jawdeh G., Niloff J., Strobel T., Swanson L., Andersen J., Ottensmeier C. CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors. J Clin Oncol. 1995 Aug;13(8):1912–1921. doi: 10.1200/JCO.1995.13.8.1912. [DOI] [PubMed] [Google Scholar]
  3. Dall P., Heider K. H., Sinn H. P., Skroch-Angel P., Adolf G., Kaufmann M., Herrlich P., Ponta H. Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer. Int J Cancer. 1995 Feb 8;60(4):471–477. doi: 10.1002/ijc.2910600408. [DOI] [PubMed] [Google Scholar]
  4. Herrlich P., Zöller M., Pals S. T., Ponta H. CD44 splice variants: metastases meet lymphocytes. Immunol Today. 1993 Aug;14(8):395–399. doi: 10.1016/0167-5699(93)90141-7. [DOI] [PubMed] [Google Scholar]
  5. Joensuu H., Ristamäki R., Klemi P. J., Jalkanen S. Lymphocyte homing receptor (CD44) expression is associated with poor prognosis in gastrointestinal lymphoma. Br J Cancer. 1993 Aug;68(2):428–432. doi: 10.1038/bjc.1993.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kainz C., Kohlberger P., Sliutz G., Tempfer C., Heinzl H., Reinthaller A., Breitenecker G., Koelbl H. Splice variants of CD44 in human cervical cancer stage IB to IIB. Gynecol Oncol. 1995 Jun;57(3):383–387. doi: 10.1006/gyno.1995.1159. [DOI] [PubMed] [Google Scholar]
  7. Kaufmann M., Heider K. H., Sinn H. P., von Minckwitz G., Ponta H., Herrlich P. CD44 variant exon epitopes in primary breast cancer and length of survival. Lancet. 1995 Mar 11;345(8950):615–619. doi: 10.1016/s0140-6736(95)90521-9. [DOI] [PubMed] [Google Scholar]
  8. Kucera H., Weghaupt K. The electrosurgical operation of vulvar carcinoma with postoperative irradiation of inguinal lymph nodes. Gynecol Oncol. 1988 Feb;29(2):158–167. doi: 10.1016/0090-8258(88)90210-7. [DOI] [PubMed] [Google Scholar]
  9. Mackay C. R., Terpe H. J., Stauder R., Marston W. L., Stark H., Günthert U. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol. 1994 Jan;124(1-2):71–82. doi: 10.1083/jcb.124.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mulder J. W., Kruyt P. M., Sewnath M., Oosting J., Seldenrijk C. A., Weidema W. F., Offerhaus G. J., Pals S. T. Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins. Lancet. 1994 Nov 26;344(8935):1470–1472. doi: 10.1016/s0140-6736(94)90290-9. [DOI] [PubMed] [Google Scholar]
  11. Salles G., Zain M., Jiang W. M., Boussiotis V. A., Shipp M. A. Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas: characterization and comparison with normal activated B cells and epithelial malignancies. Blood. 1993 Dec 15;82(12):3539–3547. [PubMed] [Google Scholar]
  12. Salmi M., Grön-Virta K., Sointu P., Grenman R., Kalimo H., Jalkanen S. Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin. J Cell Biol. 1993 Jul;122(2):431–442. doi: 10.1083/jcb.122.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Screaton G. R., Bell M. V., Jackson D. G., Cornelis F. B., Gerth U., Bell J. I. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160–12164. doi: 10.1073/pnas.89.24.12160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith C. W., Patton J. G., Nadal-Ginard B. Alternative splicing in the control of gene expression. Annu Rev Genet. 1989;23:527–577. doi: 10.1146/annurev.ge.23.120189.002523. [DOI] [PubMed] [Google Scholar]
  15. Tempfer C., Gitsch G., Haeusler G., Reinthaller A., Koelbl H., Kainz C. Prognostic value of immunohistochemically detected CD44 expression in patients with carcinoma of the vulva. Cancer. 1996 Jul 15;78(2):273–277. doi: 10.1002/(SICI)1097-0142(19960715)78:2<273::AID-CNCR13>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  16. Tempfer C., Gitsch G., Hanzal E., Reinthaller A., Koelbl H., Kainz C. Expression of the adhesion molecule CD44v3 is a prognostic factor in vulvar carcinoma. Anticancer Res. 1996 Jul-Aug;16(4A):2029–2031. [PubMed] [Google Scholar]
  17. Underhill C. CD44: the hyaluronan receptor. J Cell Sci. 1992 Oct;103(Pt 2):293–298. doi: 10.1242/jcs.103.2.293. [DOI] [PubMed] [Google Scholar]

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