Advertisement

Clinicopathologic significance of CD105-assessed microvessel density in glottic laryngeal squamous cell carcinoma

      Abstract

      Objective

      Intratumoral microvessel density (MVD) determined with the use of antibodies to endoglin (CD105) is considered to be an important prognostic marker in a variety of malignancies. The purpose of this study has been to analyze the clinicopathologic significance of CD105-assessed MVD in SCCs primary localized in glottic region of larynx.

      Methods

      Surgical specimens from 40 patients with resected glottic squamous cell carcinomas were immunostained for CD105. CD105-assessed MVD was calculated at 400× magnification. Using the mean MVD as a cut-off, tumors were classified in the “high MVD” group and in the “low MVD” group. Clinicopathologic data were collected retrospectively.

      Results

      The mean MVD assessed by CD105 in considered glottic SCCs was 12.3 (standard deviation [SD] = 3.65). MVD varied among tissue samples from 5 to 21 (median 12.5). High MVD was significantly correlated with a more aggressive tumor phenotype, including T3–T4 tumor (Fisher exact test, P = 0.004) and advanced clinical stage (Fisher exact test P = 0.026). Kruskal–Wallis test identified significant relation between pT stages and CD105-assessed MVD (P = 0.011). CD105-assessed MVD was significantly related to malignancy recurrence presence/absence (Mann–Whitney U-test P = 0.023). Logistic regression in multivariate modality showed that MVD (odds ratio [OR] 2.29, P = 0.033, 95% confidence interval [CI] 1.06–7.53) and advanced T category (T3–T4) (OR 4.11, P = 0.026, 95% CI 2.38–9.46) were significantly related to malignancy recurrence presence/absence. Cox regression analysis revealed that expression of CD105 (P = 0.031) and N status (P = 0.014) were the independent factors for disease-free survival.

      Conclusion

      High expression of CD105 correlated significantly with advanced T status and locoregional recurrence. The present preliminary results suggest that CD105-assessed MVD in primary glottic squamous cell carcinomas may identify patients at risk of disease recurrence.

      Keywords

      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:

      Subscribe to Auris Nasus Larynx
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Folkman J.
        Angiogenesis and breast cancer.
        J Clin Oncol. 1994; 12: 441-443
        • Folkman J.
        • Watson K.
        • Ingiber D.
        • Hanahan D.
        Induction of angiogenesis during the transition from hyperplasia to neoplasia.
        Nature (Lond.). 1989; 339: 58-61
        • Duff S.E.
        • Li C.
        • Garland J.M.
        • Kumar S.
        CD105 is important for angiogenesis: evidence and potential applications.
        FASEB J. 2003; 17: 984-992
        • Reinmuth N.
        • Parikh A.A.
        • Ahmad S.A.
        • Liu W.
        • Stoeltzing O.
        • Fan F.
        • et al.
        Biology of angiogenesis in tumors of the gastrointestinal tract.
        Microsc Res Tech. 2003; 60: 199-207
        • Fonsatti E.
        • Del Vecchio L.
        • Altomonte M.
        • Sigalotti L.
        • Nicotra M.R.
        • Coral S.
        • et al.
        Endoglin: an accessory component of the TGF-beta-binding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies.
        J Cell Physiol. 2001; 1888: 1-7
        • Fernandez-Ruiz E.
        • St-Jacques S.
        • Bellon T.
        • Letarte M.
        • Bernabeu C.
        Assignment of the human endoglin gene (END) to 9q34 → qter.
        Cytogenet Cell Genet. 1993; 64: 204-207
        • Li C.
        • Issa R.
        • Kumar P.
        • Hampson I.N.
        • Lopez-Novoa J.M.
        • Bernabeu C.
        • et al.
        CD105 prevents apoptosis in hypoxic endothelial cells.
        J Cell Sci. 2003; 116: 2677-2685
        • Dales J.P.
        • Garcia S.
        • Carpentier S.
        • Andrac L.
        • Ramuz O.
        • Lavaut M.N.
        • et al.
        Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression.
        Hum Pathol. 2004; 35: 176-183
        • Kumar S.
        • Ghellal A.
        • Li C.
        • Byrne G.
        • Haboubi N.
        • Wang J.M.
        • et al.
        Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis.
        Cancer Res. 1999; 59: 856-861
        • Massi D.
        • Franchi A.
        • Paglierani M.
        • Ketabchi S.
        • Borgognoni L.
        • Reali U.M.
        • et al.
        Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma.
        Hum Pathol. 2004; 35: 496-502
        • Li C.
        • Gardy R.
        • Seon B.K.
        • Duff S.E.
        • Abdalla S.
        • Renehan A.
        • et al.
        Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis.
        Br J Cancer. 2003; 88: 1424-1431
        • Saad R.S.
        • Liu Y.L.
        • Nathan G.
        • Celebrezze J.
        • Medich D.
        • Silverman J.F.
        Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer.
        Mod Pathol. 2004; 17: 197-203
        • Yu J.X.
        • Zhang X.T.
        • Liao Y.Q.
        • Zhang Q.Y.
        • Chen H.
        • Lin M.
        • et al.
        Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance.
        World J Gastroenterol. 2003; 9: 2866-2869
        • Li S.L.
        • Gao D.L.
        • Zhao Z.H.
        • Liu Z.W.
        • Zhao Q.M.
        • Yu J.X.
        • et al.
        Correlation of matrix metalloproteinase suppressor genes RECK, VEGF, and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma.
        World J Gastroenterol. 2007; 13: 6076-6081
        • Mineo T.C.
        • Ambrogi V.
        • Baldi A.
        • Rabitti C.
        • Bollero P.
        • Vincenzi B.
        • et al.
        Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumor vessel invasion after radical surgery for IB-IIA non-small cell lung cancer.
        J Clin Pathol. 2004; 57: 591-597
        • Tanaka F.
        • Otake Y.
        • Yanagihara K.
        • Kawano Y.
        • Miyahara R.
        • Li M.
        • et al.
        Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody.
        Clin Cancer Res. 2001; 7: 3410-3415
        • Saad R.S.
        • Jasnosz K.M.
        • Tung M.Y.
        • Silverman J.F.
        Endoglin (CD105) expression in endometrial carcinoma.
        Int J Gynecol Pathol. 2003; 22: 248-253
        • Salvesen H.B.
        • Gulluoglu M.G.
        • Stefansson I.
        • Akslen L.A.
        Significance of CD 105 expression for tumor angiogenesis and prognosis in endometrial carcinomas.
        APMIS. 2003; 111: 1011-1018
        • Yagasaki H.
        • Kawata N.
        • Takimoto Y.
        • Nemoto N.
        Histopathological analysis of angiogenic factors in renal cell carcinoma.
        Int J Urol. 2003; 10: 220-227
        • Chien C.Y.
        • Su C.Y.
        • Hwang C.F.
        • Chuang H.C.
        • Hsiao Y.C.
        • Wu S.L.
        • et al.
        Clinicopathologic significance of CD105 expression in squamous cell carcinoma of the hypopharynx.
        Head Neck. 2006; 28: 441-446
        • Marioni G.
        • Gaio E.
        • Giacomelli L.
        • Marchese-Ragona R.
        • Staffieri C.
        • Staffieri A.
        • et al.
        Endoglin (CD105) expression in head and neck basaloid squamous cell carcinoma.
        Acta Otolaryngol. 2005; 125: 307-311
        • Martone T.
        • Rosso P.
        • Albera R.
        • Migliaretti G.
        • Fraire F.
        • Pignataro L.
        • et al.
        Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome.
        Oral Oncol. 2005; 41: 147-155
        • Nagatsuka H.
        • Hibi K.
        • Gunduz M.
        • Tsujigiwa H.
        • Tamamura R.
        • Sugahara T.
        • et al.
        Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas.
        J Oral Pathol Med. 2005; 34: 70-76
        • Kyzas P.A.
        • Agnantis N.J.
        • Stefanou D.
        Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma.
        Virchows Arch. 2006; 448: 768-775
        • Pruneri G.
        • Ponzoni M.
        • Ferreri A.J.
        • Decarli N.
        • Tresoldi M.
        • Raggi F.
        • et al.
        Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients.
        Br J Haematol. 2002; 118: 817-820
        • Pruneri G.
        • Bertolini F.
        • Baldini L.
        • Valentini S.
        • Goldaniga M.
        • Soligo D.
        • et al.
        Angiogenesis occurs in hairy cell leukaemia (HCL) and in NOD/SCID mice transplanted with the HCL line Bonna-12.
        Br J Haematol. 2003; 120: 695-698
        • Weidner N.
        • Semple J.P.
        • Welch W.R.
        • Folkman J.
        Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma.
        N Engl J Med. 1991; 324: 1-8
        • Altman D.G.
        • Lausen B.
        • Sauerbrei W.
        • Schumacher M.
        Dangers of using “optimal” cutpoints in the evaluation of prognostic factors.
        J Natl Cancer Inst. 1994; 86: 829-835
        • Mietinnen M.
        • Lindenmayer A.E.
        • Chaubal A.
        Endothelial cell markers CD31, CD34, BNH9 antibody to H- and Y-antigens: evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor.
        Mod Pathol. 1994; 7: 82-90
        • Lindenmayer A.E.
        • Miettinen M.
        Immunophenotypic features of uterine stromal cells. CD34 expression in endocervical stroma.
        Virchows Arch. 1995; 426: 457-460
        • Emoto M.
        • Iwasaki H.
        • Mimura K.
        • Kawarabayashi T.
        • Kikuchi M.
        Difference in the angiogenesis of benign and malignant ovarian tumors, demonstrated by analyses of solor Doppler ultrasound, immunohistochemistry, and microvessel density.
        Cancer. 1997; 80: 899-907
        • Akagi K.
        • Ikeda Y.
        • Sumiyoshi Y.
        • Kimura Y.
        • Kinoshita J.
        • Miyazaki M.
        • et al.
        Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development.
        Surgery. 2002; 131: S109-S113
        • Guidi A.J.
        • Fischer L.
        • Harris J.R.
        • Schnitt S.J.
        Microvessel density and distribution in ductal carcinoma in situ of the breast.
        J Natl Cancer Inst. 1994; 86: 614-619
        • Wikstrom P.
        • Lissbrant I.F.
        • Stattin P.
        • Egevad L.
        • Bergh A.
        Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer.
        Prostate. 2002; 51: 268-275
        • Brewer C.A.
        • Setterdahl J.J.
        • Li M.J.
        • Johnston J.M.
        • Mann J.L.
        • McAsey M.E.
        Endoglin expression as a measure of microvessel density in cervical cancer.
        Obstet Gynecol. 2000; 96: 224-228
        • Schimming R.
        • Marme D.
        Endoglin (CD105) expression in squamous cell carcinoma of the oral cavity.
        Head Neck. 2002; 24: 151-156
        • Mărgăritescu C.
        • Simionescu C.
        • Mogoantă L.
        • Badea P.
        • Pirici D.
        • Stepan A.
        • et al.
        Endoglin (CD105) and microvessel density in oral squamous cell carcinoma.
        Rom J Morphol Embryol. 2008; 49: 321-326
        • Marioni G.
        • Marino F.
        • Giacomelli L.
        • Staffieri C.
        • Mariuzzi M.L.
        • Violino E.
        • et al.
        Endoglin expression is associated with poor oncologic outcome in oral and oropharyngeal carcinoma.
        Acta Otolaryngol (Stockh). 2006; 126: 633-639
        • Chuang H.C.
        • Su C.Y.
        • Huang H.Y.
        • Chien C.Y.
        • Chen C.M.
        • Huang C.C.
        High expression of CD105 as a prognostic predictor of early tongue cancer.
        Laryngoscope. 2006; 116: 1175-1179
        • Marioni G.
        • Ottaviano G.
        • Giacomelli L.
        • Staffieri C.
        • Casarotti-Todeschini S.
        • Bonandini E.
        • et al.
        CD105-assessed micro-vessel density is associated with malignancy recurrence in laryngeal squamous cell carcinoma.
        Eur J Surg Oncol. 2006; 32: 1149-1153
        • Marioni G.
        • Giacomelli L.
        • D’Alessandro E.
        • Staffieri C.
        • Guzzardo V.
        • Staffieri A.
        • et al.
        Laryngeal carcinoma recurrence rate and disease-free interval are related to CD105 expression but not to vascular endothelial growth factor 2 (Flk-1/Kdr) expression.
        Anticancer Res. 2008; 28: 551-557