Intensity of cervical inflammatory reaction as a risk factor for recurrence of carcinoma of the uterine cervix in stages IB and IIA
Keywords:
Uterine cervical neoplasms, Recurrence, Survival, Inflammation, Lymphatic metastasis, Neoplasm invasivenessAbstract
CONTEXT AND OBJECTIVE: Infl ammatory reaction intensity has been indicated as a possible recurrence risk factor in carcinoma of the uterine cervix. Some authors observed greater risk with weak infl ammatory reaction, while others described the opposite. This study aimed to evaluate risk factors for initial-stage uterine cervix carcinoma recurrence (IB and IIA), considering infl ammatory reaction intensity. DESIGN AND SETTING: Retrospective cohort at Hospital do Câncer A. C. Camargo. METHODS: 289 patients with diagnosed uterine cervix carcinoma (stages IB and IIA) who underwent radical surgery between 1980 and 1999 were studied. Data were collected from medical records. Histological sections from tumors and lymph nodes could be reviewed in 247 cases. Five-year disease-free survival rates were calculated using the Kaplan-Meier method and curves were compared using the log-rank test. Cox’s proportional-hazards model was used for multivariate analysis. Recurrence risk was estimated using hazard ratios (HR). RESULTS: Forty-three recurrences were found. Multivariate analysis identifi ed the following independent recurrence risk factors: number of metastatic pelvic lymph nodes (one lymph node: HR = 3.3 [1.3-8.3]; two or three: HR = 5.3 [1.5- 18.6]; four or more: HR = 7.6 [1.7-33.2]), tumor invasion depth (deepest third: HR = 2.1 [1.1-4.1]) and infl ammatory reaction intensity in the uterine cervix (absent or slight: HR = 2.5 [1.1-5.7]). CONCLUSION: This study identifi ed that absent or slight infl ammatory reaction was an independent risk factor for recurrence. The other risk factors were the number of metastatic pelvic lymph nodes and invasion of the deepest third of the uterine cervix.
Downloads
References
Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001;37(Suppl 8):S4-66.
Benedet JL, Odicino F, Maisonneuve P, et al. Carcinoma of the cervix uteri. Int J Gynaecol Obstet. 2003;83(Suppl 1):41-78.
Piver MS, Rutledge F, Smith JP. Five classes of extended hys- terectomy for women with cervical cancer. Obstet Gynecol. 1974;44(2):265-72.
Wilkinson EJ, Malik S. National Institutes of Health Consensus Development Conference statement on cervical cancer. April 1-3, 1996. J Womens Health. 1998;7(5):604-5.
Chi DS, Gemignani ML, Curtin JP, Hoskins WJ. Long-term experience in the surgical management of cancer of the uterine cervix. Semin Surg Oncol. 1999;17(3):161-7.
Wang CJ, Lai CH, Huang HJ, et al. Recurrent cervical car- cinoma after primary radical surgery. Am J Obstet Gynecol. 1999;181(3):518-24.
Hart K, Han I, Deppe G, et al. Postoperative radiation for cervical cancer with pathologic risk factors. Int J Radiat Oncol Biol Phys. 1997;37(4):833-8.
Fregnani JHTG. Doença micrometastática nos linfonodos pélvicos no carcinoma do colo do útero: diagnóstico e risco de recorrência. [thesis]. São Paulo: Fundação Antônio Prudente— Hospital A. C. Camargo; 2005.
van Nagell JR Jr, Donaldson ES, Wood EG, Parker JC Jr. The significance of vascular invasion and lymphocytic infiltration in invasive cervical cancer. Cancer. 1978;41(1):228-34.
Stendahl U, Willen H, Willen R. Classification and grading of invasive squamous cell carcinoma of the uterine cervix. Acta Radiol Oncol Radiat Phys Biol. 1979;18(6):481-96.
Stendahl U, Eklund G, Willen R. Invasive squamous cell car- cinoma of the uterine cervix. IV. Analysis of a histopathologic malignancy grading system and construction of a partial index. Acta Radiol Oncol. 1981;20(5):289-4.
Pagnini CA, Della Palma P, De Laurentiis G. Malignancy grading in squamous carcinoma of uterine cervix treated by surgery. Br J Cancer. 1980;41(3):415-21.
Willen H, Eklund G. Invasive squamous cell carcinoma of the uterine cervix. IX. Construction of a partial index in a histopathologic malignancy grading system. Acta Radiol Oncol. 1985;24(2):133-8.
Reinthaller A, Tatra G, Breitenecker G, Janisch H. Prognosefak- toren beim invasiven Zervixkarzinom der Stadien Ia-IIb nach radikaler Hysterektomie unter besonderer Berücksichtigung der Stromareaktion. [Prognostic factors in stage Ia-IIb invasive cervix cancer after radical hysterectomy with special reference to stroma reaction]. Geburtshilfe Frauenheilkd. 1991;51(10):809-13.
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(5B):2245-8.
Bethwaite PB, Holloway LJ, Thornton A, Delahunt B. In- filtration by immunocompetent cells in early stage invasive carcinoma of the uterine cervix: a prognostic study. Pathology. 1996;28(4):321-7.
Kristensen GB, Abeler VM, Risberg B, Trop C, Bryne M. Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma. Gynecol Oncol. 1999;74(2):245-51.
Chao HT, Wang PH, Tseng JY, Lai CR, Chiang SC, Yuan CC. Lymphocyte-infiltrated FIGO Stage IIB squamous cell carcinoma of the cervix is a prominent factor for disease-free survival. Eur J Gynaecol Oncol. 1999;20(2):136-40.
Graflund M, Sorbe B, Hussein A, Bryne M, Karlsson M. The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix. Int J Gynecol Cancer. 2002;12(1):32-41.
Horn LC, Raptis G, Nenning H. DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b. Anal Quant Cytol Histol. 2002;24(1):23-9.
Yamazawa K, Matsui H, Ishikura H, Seki K, Mitsuhashi A, Sekiya S. Significance of perivascular lymphocytic infiltrates on survival of patients with invasive cervical cancer. J Immunother (1997). 2003;26(2):149-55.
Gauthier P, Gore I, Shingleton HM, Soong SJ, Orr JW Jr, Hatch KD. Identification of histopathologic risk groups in stage IB squamous cell carcinoma of the cervix. Obstet Gynecol. 1985;66(4):569-74.
Berman ML, Bergen S, Salazar H. Influence of histological features and treatment on the prognosis of patients with cervi- cal cancer metastatic to pelvic lymph nodes. Gynecol Oncol. 1990;39(2):127-31.
Zaino RJ, Ward S, Delgado G, et al. Histopathologic predic- tors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. Cancer. 1992;69(7):1750-8.
Samlal RA, van der Velden J, Ten Kate FJ, Schilthuis MS, Hart AA, Lammes FB. Surgical pathologic factors that predict recurrence in stage IB and IIA cervical carcinoma patients with negative pelvic lymph nodes. Cancer. 1997;80(7):1234-40.
Botti C, Seregni E, Ferrari L, Martinetti A, Bombardieri E. Immunosuppressive factors: role in cancer development and progression. Int J Biol Markers. 1998;13(2):51-69.
Elgert KD, Alleva DG, Mullins DW. Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol. 1998;64(3):275-90.
Melo FHM, Junqueira MS, Chammas R. Mecanismos de invasão e metástases. In: Brentani MM, Coelho FRG, Kowalski LP, editors. Bases da oncologia. 2nd ed. São Paulo: Lemar; 2003. p. 202-26.
Singh N, Arif S. Histopathologic parameters of prognosis in cervi- cal cancer--a review. Int J Gynecol Cancer. 2004;14(5):741-50.
Sevin BU, Lu Y, Bloch DA, Nadji M, Koechli OR, Averette HE. Surgically defined prognostic parameters in patients with early cervical carcinoma. A multivariate survival tree analysis. Cancer. 1996;78(7):1438-46.
Tsai CS, Lai CH, Wang CC, et al. The prognostic factors for patients with early cervical cancer treated by radical hys- terectomy and postoperative radiotherapy. Gynecol Oncol. 1999;75(3):328-33.
Ishikawa H, Nakanishi T, Inoue T, Kuzuya K. Prognostic fac- tors of adenocarcinoma of the uterine cervix. Gynecol Oncol. 1999;73(1):42-6.
Aoki Y, Sasaki M, Watanabe M, et al. High-risk group in node- positive patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation. Gynecol Oncol. 2000;77(2):305-9.
Fregnani JHTG. Proposta de escore preditivo de recorrência em pacientes submetidas a tratamento cirúrgico radical do carcinoma do colo do útero estádios IB e IIA. [Proposal of a predictive recurrence score in patients submitted to radical surgical treatment of stage IB and IIA carcinoma of the cervix uteri]. Rev Bras Ginecol Obstet. 2003;25(9):694-5.
Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1990;38(3):352-7.
Kamura T, Tsukamoto N, Tsuruchi N, et al. Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy. Cancer. 1992;69(1):181-6.
Lai CH, Hong JH, Hsueh S, et al. Preoperative prognostic variables and the impact of postoperative adjuvant therapy on the outcomes of Stage IB or II cervical carcinoma patients with or without pelvic lymph node metastases: an analysis of 891 cases. Cancer. 1999;85(7):1537-46.
Novaes PE, Cruz EA. Tumores ginecológicos. In: Pellizon ACA, Salvajoli JV, Maia MAC, Novaes PERS, Fogaroli RC, Ferrigno R, editors. Rotinas e condutas em radioterapia. 2nd ed. São Paulo: Lemar; 2002. p. 57-63.
