Relevance of micrometastases detected by reverse transcriptase-polymerase chain reaction for melanoma recurrence
systematic review and meta-analysis
Keywords:
Reverse transcriptase, Polymerase chain reaction, Sentinel node, Melanoma, Micrometastasis, ImmunohistochemistryAbstract
CONTEXT: Cutaneous melanoma presents significant morbidity and mortality. Nowadays, about 90% of them are diagnosed by clinical examination and most are localized melanomas. Sentinel node biopsy has brought about a new and interesting approach towards localized cutaneous melanoma. The meaning of micrometastases in sentinel nodes diagnosed by the reverse transcriptase-polymerase chain reaction is not well established. OBJECTIVE: To define the real value of micrometastases diagnosed by the reverse transcriptase-polymerase chain reaction in relation to melanoma recurrence. METHODS: Systematic literature review and meta-analysis. The Cochrane Library, Medline, Embase and Lilacs were the databases searched. We used the following key words: sentinel node and melanoma; sentinel node and reverse transcriptase-polymerase chain reaction; melanoma and reverse transcriptase-polymerase chain reaction. Cohort studies enrolling localized cutaneous melanoma patients who underwent sentinel node biopsy were selected. Sentinel node evaluations included hematoxylin and eosin, immunohistochemistry and reverse transcriptase-polymerase chain reaction. RESULTS: Out of the 1,542 studies evaluated, four were eligible. The four studies, when combined, were statistically homogeneous. The sample totaled 450 patients grouped as follows: 163 with a sentinel node negative to hematoxylin eosin and immunohistochemistry and positive to the reverse transcriptase-polymerase chain reaction; 192 with a sentinel node negative to hematoxylin eosin, immunohistochemistry and the reverse transcriptase-polymerase chain reaction and 95 patients with a sentinel node positive to hematoxylin eosin and/ or immunohistochemistry. We analyzed the first two groups. The meta-analysis for the random model showed an increased effect from a positive reverse transcriptase-polymerase chain reaction on the recurrence rate. A similar result occurred in the meta-analysis for the fixed effect model. CONCLUSION: Patients with a positive reverse transcriptase-polymerase chain reaction had a greater recurrence rate than those with a negative reverse transcriptase-polymerase chain reaction. This suggests an important role for the reverse transcriptase-polymerase chain reaction in sentinel node examinations. In view of the small sample, a clinical trial could better evaluate this question.
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References
Brozena SJ, Fenske NA, Perez IR. Epidemiology of malignant melanoma, worldwide incidence, and etiologic factors. Semin Surg Oncol 1993;9(3):165-7.
Oliveira Filho RS, Ferreira LM, Barbieri A, et al. Linfa- denectomia seletiva com biópsia de linfonodo sentinela no melanoma cutâneo. Experiência brasileira Projeto FAPESP 97/02516-0. An bras dermatol 2000;75:573-80.
Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the Ameri- can Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001;19(16):3622-34.
Heller R, Becker J, Wasselle J, et al. Detection of submicro- scopic lymph node metastases in patients with melanoma. Arch Surg 1991;126(12):1455-9.
Morton DL, Wen D, Cochran AJ. Management of early stage melanoma by intraoperative lymphatic mapping and selective lymphadenectomy: An alternative to routine elective lym- phadenectomy or “watch and wait”. Surg Oncol Clin North Am 1992;1:247-59.
Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma.
Arch Surg 1992;127(4):392-9.
Smart KR, Cahoon BW, Dale PS. Sentinel lymphadenectomy for staging patients with intermediate-level melanoma. Ann Surg 2000;66(3):280-3.
Messina JL, Glass LF, Cruse CW, Berman C, Ku NK, Reintgen DS. Pathologic examination of the sentinel lymph node in malignant melanoma. Am J Surg Pathol 1999;23(6):686-90.
Wang X, Heller R, VanVoorhis N, et al. Detection of submi- croscopic lymph node metastases with polymerase chain reac- tion in patients with malignant melanoma. Ann Surg 1994;220(6):768-74.
Lukowsky A, Bellmann B, Ringk A, et al. Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction. J Invest Dermatol 1999;113(4):554-9.
Van der Velde-Zimmermann D, Roijers JF, Bouwens-Rombouts A, et al. Molecular test for the detection of tumor cells in blood and sentinel nodes of melanoma patients. Am J Pathol 1996;149(3):759-64.
Keilholz U, Willhauck M, Rimoldi D, et al. Realiability of re- verse transcription-polymerase chain reaction (RT-PCR)-based assays for the detection of circulating tumour cells: a quality- assurance initiative of the EORTC Melanoma Cooperative Group. Eur J Cancer 1998;34(5):750-3.
Goydos JS, Ravikumar TS, Germino FJ, Yudd A, Bancila E. Minimally invasive staging of patients with melanoma: sentinel lymphadenectomy and detection of the melanoma-specific pro- teins MART-1 and tyrosinase by reverse transcriptase polymer- ase chain reaction. J Am Coll Surg 1998;187(2):182-8.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Con- trol Clin Trials. 1986;7(3):177-88.
Demets DL. Methods for combining randomized clinical tri- als: strengths and limitations. Stat Med 1987;6(3):341-50.
The Nordic Cochrane Centre. Cochrane Collaboration. Review Manager. Powered by the Cochrane Collaboration. RevMan. Ver- sion 4.1-c. Available at http://www.cochrane-net.org/revman/.
Dickersin K, Scherer R, Lefebvre C. Identifying relevant stud- ies for systematic reviews. BMJ 1994;309(6964):1286-91.
Olsen O, Middleton P, Ezzo J, et al. Quality of Cochrane re- views: assessment of sample from 1998. BMJ 2001;323:829-32.
Joseph E, Messina J, Glass FL, et al. Radioguided surgery for the ultrastaging of the patient with melanoma. Cancer J Sci Am. 1997;3(6):341-5.
Bostick PJ, Morton DL, Turner RR, et al. Prognostic signifi- cance of occult metastases detected by sentinel lymphadenec- tomy and reverse transcriptase-polymerase chain reaction in early-stage stage melanoma patients. J Clin Oncol 1999;17(10):3238-44.
Blaheta HJ, Ellwanger U, Schittek B, et al. Examination of regional lymph nodes by sentinel node biopsy and molecular analysis provides new staging facilities in primary cutaneous melanoma. J Invest Dermatol. 2000;114(4):637-42.
Li W, Stall A, Shivers SC, et al. Clinical relevance of molecular staging for melanoma comparison of RT-PCR and immuno- histochemistry staining in sentinel lymph nodes of patients with melanoma. Ann Surg 2000;231(6):795-803.
Blaheta HJ, Schittek B, Breuninger H, et al. Detection of melanoma micrometastasis in sentinel nodes by reverse tran- scription-polymerase chain reaction correlates with tumor thick- ness and is predictive of micrometastatic disease in the lymph node basin. Am J Surg Pathol 1999;23(7) 822-8.
Pellegrino D, Bellina CR, Manca G, et al. Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohisto- chemistry. Tumori 2000;86(4):336-8.
van der Velde-Zimmermann D, Schipper ME, de Weger RA, Hennipman A, Borel Rinkes IH. Sentinel node biopsies in melanoma patients: a protocol for accurate, efficient, and cost- effective analysis by preselection for immunohistochemistry on the basis of Tyr-PCR. Ann Surg Oncol 2000;7(1):51-4.
McMasters KM. The Sunbelt Melanoma Trial. Ann Surg Oncol 2001;8(9Suppl):41S-43S.