Skip to main content

Advertisement

SpringerLink
Log in

Clinical Value of Immunohistochemically Detected Lymphovascular Space Invasion in Early Stage Cervical Carcinoma

  • Gynecologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This study investigates the clinical significance of lymphovascular space invasion (LVSI) as detected by hematoxylin and eosin (LVSI-H&E) and immunohistochemistry (LVSI-IHC) in early stage cervical carcinoma.

Methods

Single representative sections from 97 patients with early stage squamous cell cervical cancer were immunostained with pancytokeratin and CD31 endothelial cell marker antibodies. The H&E sections and their corresponding immunostained sections were reexamined to identify LVSI. Associations between LVSI with clinicopathological factors were sought.

Results

Overall, LVSI was present in 29 (29.9%) and absent in 68 (70.1%) by IHC, as compared with 18 cases (18.6%) and 79 cases (81.4%), respectively, by H&E. Statistical analysis revealed a significant association between LVSI-H&E and nodal metastasis (P = .004). Follow-up data were available for 76 patients. The median follow-up period was 64 months. During follow-up, 7 of 24 patients with recurrent disease had evidence of LVSI-H&E as opposed to 3 of 52 cases with no recurrence. There was a significant association between tumor recurrence and LVSI-H&E (P = .009). The 5-year recurrence-free survival was 30% for the group with LVSI-H&E compared with 73% without. There was a significant difference in the recurrence-free survival between the two groups (P = .002). In contrast LVSI-IHC was found to be associated with no pathological factors, and survival analysis revealed no statistically significant association with recurrence or survival.

Conclusion

LVSI-H&E in early stage cervical cancer remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event and seems to be of no clinical value.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Franco EL, Schlecht NF, Saslow D. The epidemiology of cervical cancer. Cancer J 2003;9:348–59.

    Article  PubMed  Google Scholar 

  2. Delgado G, Bundy B, Zaino R, et al. Prospective surgical-pathologic study of disease-free interval in patients with stage Ib squamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1990;38:352–7.

    Article  PubMed  CAS  Google Scholar 

  3. Alvarez RD, Soong SJ, Kinney WK, et al. Identification of prognostic factors and risk groups in patients found to have nodal metastases at the time of radical hysterectomy for early stage squamous carcinoma of the cervix. Gynecol Oncol 1989;35:130–5.

    Article  PubMed  CAS  Google Scholar 

  4. Delgado G, Bundy BN, Fowler WC, et al. A prospective surgical pathologic study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1989;35:314–20.

    Article  PubMed  CAS  Google Scholar 

  5. Fujisawa T, Yamaguchi Y, Saitoh Y, et al. Blood and lymphatic vessel invasion as prognostic factors for patients with primary resected non small cell carcinoma of the lung with intrapulmonary metastases. Cancer 1995;76:2464–70.

    Article  PubMed  CAS  Google Scholar 

  6. Katz A, Strom EA, Buchholz TA, et al. The influence of pathologic tumor characteristics on locoregional recurrence rates following mastectomy. Int J Radiat Oncol Biol Phys 2001;50:735–42.

    Article  PubMed  CAS  Google Scholar 

  7. Atasii T, Aksu MF, Cetinkaya MB. Prognostic factors that affect survival after the treatment of early stage cervical carcinoma. Int Surg 2000;85:147–51.

    PubMed  CAS  Google Scholar 

  8. Sakuragi N, Takeda N, Hareyama H, et al. A multivariate analysis of blood vessel and lymph vessel invasion as predictors of ovarian and lymph node metastases in patients with cervical carcinoma. Cancer 2000;88:2578–83.

    Article  PubMed  CAS  Google Scholar 

  9. Zaino RJ, Ward S, Delgado G, et al. Histopathologic predictors of the behaviour of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. Cancer 1992;69:1750–8.

    Article  PubMed  CAS  Google Scholar 

  10. Morice P, Piovesan P, Rey A, et al. Prognostic value of lymphovascular space invasion determined with hematoxylin-eosin staining in early stage cervical carcinoma: results of a multivariate analysis. Ann Oncol 2003;14:1511–7.

    Article  PubMed  CAS  Google Scholar 

  11. Silva-Filho AL, Reis FM, Traiman P, et al. Clinicopathological features influencing pelvic lymph node metastasis and vaginal and parametrial involvement in patients with carcinoma of the cervix. Gynecol Obstet Invest 2005;59:92–6.

    Article  PubMed  Google Scholar 

  12. Werner-Wasik M, Schmid CH, Bornstein L, et al. Prognostic factors for local and distant recurrence in stage I and II cervical carcinoma. Int J Radiat Oncol Biol Phys 1995;32:1309–17.

    PubMed  CAS  Google Scholar 

  13. Sykes P, Allen D, Cohen C, et al. Does the density of lymphatic vascular space invasion affect the prognosis of stage Ib and IIA node negative carcinoma of the cervix? Int J Gynecol Cancer 2993;13:313–6.

    Article  Google Scholar 

  14. Comerci G, Bolger BS, Flanelly G, et al. Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix with negative lymph nodes. Int J Gynecol Cancer 1998;8:23–6.

    Article  PubMed  Google Scholar 

  15. Kainz C, Gitsch G, Tempfer C, et al. Vascular space invasion and inflammatory stromal reaction as prognostic factors in patients with surgically treated cervical cancer stage IB to IIB. Anticancer Res 1994;14:2245–8.

    PubMed  CAS  Google Scholar 

  16. Grisaru DA, Covens A, Franssen E, et al. Histopathologic score predicts recurrence free survival after radical surgery in patients with stage IA2-IB1–2 cervical carcinoma. Cancer 2003;97:1904–8.

    Article  PubMed  Google Scholar 

  17. Ayhan A, Al RA, Baykal C, et al. Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy. Int J Gynecol Cancer 2004;14:286–92.

    Article  PubMed  CAS  Google Scholar 

  18. Takeda N, Sakuragi N, Takeda M, et al. Multivariate analysis of histopathological prognostic factors in invasive cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Acta Obstet Gynecol Scand 2002;81:1144–51.

    Article  PubMed  Google Scholar 

  19. Alexander-Sefre F, Singh N, Ayhan A, et al. Detection of tumour lymphovascular space invasion using dual cytokeratin and CD-31 immunohistochemistry. J Clin Pathol 2003;56:786–8.

    Article  PubMed  CAS  Google Scholar 

  20. Alexander-Sefre F, Singh N, Ayhan A, et al. Clinical value of immunohistochemically detected lymphovascular space invasion in endometrioid endometrial cancer. Gynecol Oncol 2004;92:653–9.

    Article  PubMed  CAS  Google Scholar 

  21. Pecorelli S, Benedet JL, Creasman WT, et al. FIGO staging of gynaecologic cancer 1994–1997 FIGO committee on gynaecologic oncology. International federation of gynecology and obstetrics. Int J Gynaecol Obstet 1999;64:5–10.

    Article  PubMed  CAS  Google Scholar 

  22. Roman LD, Felix JC, Muderspach LI, et al. Influence of quantity of lymph-vascular space invasion on the risk of nodal metastases in women with early-stage squamous cancer of the cervix. Gynecol Oncol 1998;68:220–5.

    Article  PubMed  CAS  Google Scholar 

  23. Ho CM, Chien TY, Huang SH, et al. Multivariate analysis of the prognostic factors and outcomes in early cervical cancer patients undergoing radical hysterectomy. Gynecol Oncol 2004;c93:458–64.

    Article  Google Scholar 

  24. Kamelle SA, Rutledge TL, Tillmanns TD, et al. Surgical-pathological predictors of disease-free survival and risk groupings for IB2 cervical cancer: do the traditional models still apply? Gynecol Oncol 2004;94:249–55.

    Article  PubMed  Google Scholar 

  25. Birner P, Obermair A, Schindl M, et al. Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer. Clin Cancer Res 2001;7:93–7.

    PubMed  CAS  Google Scholar 

  26. Tsuruchi N, Kaku T, Kamura T, et al. The prognostic significance of lymphovascular space invasion in endometrial cancer when conventional hematoxylin and eosin staining is compared to immunohistochemical staining. Gynecol Oncol 1995;57:307–12.

    Article  PubMed  CAS  Google Scholar 

  27. Obermair A, Wanner C, Bilgi S, et al. The influence of vascular space involvement on the prognosis of patients with stage IB cervical carcinoma: correlation of results from hematoxylin and eosin staining with results from immunostaining for factor VIII–related antigen. Cancer 1998;82:689–96.

    Article  PubMed  CAS  Google Scholar 

  28. Birner P, Obermair A, Schindl M, et al. Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer. Clin Cancer Res 2001;7:93–7.

    PubMed  CAS  Google Scholar 

  29. Chernofsky MR, Felix JC, Muderspach LI, et al. Influence of quantity of lymph vascular space invasion on time to recurrence in women with early-stage squamous cancer of the cervix. Gynecol Oncol 2006;100:288–93.

    Article  PubMed  Google Scholar 

  30. Podgrabinska S, Braun P, Velasco P, et al. Molecular characterization of lymphatic endothelial cells. Proc Natl Acad Sci USA 2002;99:16069–74.

    Article  PubMed  CAS  Google Scholar 

  31. RayChaudhury A, Elkins M, Kozien D, et al. Regulation of PECAM-1 in endothelial cells during cell growth and migration. Exp Biol Med (Maywood) 2001;226:686–91.

    CAS  Google Scholar 

  32. Zehnder JL, Hirai K, Shatsky M, et al. The cell adhesion molecule CD31 is phosphorylated after cell activation. Down-regulation of CD31 in activated T lymphocytes. J Biol Chem 1992;267:5243–9.

    PubMed  CAS  Google Scholar 

  33. Mohammed RA, Martin SG, Gill MS, et al. Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol 2007;31:1825–33.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors thank the Cancer Research-UK for awarding an elective bursary for this study.

Author information

Authors and Affiliations

  1. Cancer Research-United Kingdom Translational Oncology Laboratory, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, John Vane Building, Charterhouse Square, London, EC1M 6BQ, UK

    Chung Sim Lim MRCS & Haytham Al-Rawi BMedSci, MRCP

  2. Glasgow Royal Infirmary, Castle Street, Glasgow, G4 0SF, UK

    Farhad Alexander-Sefre MRCOG, MD

  3. Wishaw General Hospital, 50 Netherton Street, Wishaw, ML2 0DP, UK

    Mohamed Allam MSc, MRCOG

  4. Department of Pathology, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, EC1A 7BE, UK

    Naveena Singh FRCPath & Joanne Chin Aleong FRCPath

  5. Institute for Women’s Health, University College London, Huntley Street, London, WC1E 6DH, UK

    Ian J. Jacobs MD, MRCOG

Authors
  1. Chung Sim Lim MRCS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farhad Alexander-Sefre MRCOG, MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed Allam MSc, MRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naveena Singh FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joanne Chin Aleong FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haytham Al-Rawi BMedSci, MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ian J. Jacobs MD, MRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chung Sim Lim MRCS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lim, C.S., Alexander-Sefre, F., Allam, M. et al. Clinical Value of Immunohistochemically Detected Lymphovascular Space Invasion in Early Stage Cervical Carcinoma. Ann Surg Oncol 15, 2581–2588 (2008). https://doi.org/10.1245/s10434-008-0014-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-008-0014-z

Keywords

Search

Navigation