Prognostic significance of molecular staging study of sentinel lymph nodes by reverse transcriptase-polymerase chain reaction for tyrosinase in melanoma patients.
ABSTRACT We performed this study to evaluate the clinical effect of microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from patients with early-stage melanoma.
Patients with confirmed cutaneous melanoma (American Joint Committee on Cancer stages I and II) underwent standard lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45 and molecular analysis by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase (using beta-actin as a control).
Of 180 patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1), and 142 (79%) had negative histological results. Analysis by RT-PCR detected tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the analysis of recurrence (mean follow-up, 45 months), only 18 patients had a recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37 in group 3. No recurrences were seen in group 4. Only group 1 had a significantly shorter disease-free survival and overall survival compared with the other groups.
After a long follow-up period, molecular upstaging by tyrosinase RT-PCR failed to detect a subgroup of patients with an increased probability of recurrence.
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ABSTRACT: The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.Tumori 95(3):298-302. · 1.09 Impact Factor
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ABSTRACT: Sentinel lymph node evaluation has enabled identification of patients with cutaneous melanoma who might benefit from elective regional lymph node dissection. Sentinel nodes are currently assessed by histologic and reverse transcription polymerase chain reaction (RT-PCR) evaluation for melanocyte-specific markers. The clinical significance of positive findings by RT-PCR in the absence of histologic evidence of metastasis (HIS(NEG)/PCR(POS)) remains unclear. Examination of 264 lymph nodes from 139 patients revealed histopathologic positivity in 34 patients (24.5%), in which 26 also demonstrated simultaneous RT-PCR positivity (HIS(POS)/PCR(POS)). Of 35 HIS(NEG)/PCR(POS) patients (25.2%), five also had nodal capsular nevi. In total, capsular nevi were detected in 13 patients (9.4%). A total of 70 patients (50.4%) had negative sentinel nodes by both histopathology and RT-PCR (HIS(NEG)/PCR(NEG)). Over a median follow-up of 25 months, local and/or systemic recurrence developed in 31 patients (22.3%). Recurrence rates were similar among patients with histopathologic evidence of sentinel lymph node metastasis, irrespective of RT-PCR status (HIS(POS)/PCR(POS) 62%; HIS(POS)/PCR(NEG) 75%). In contrast, only 10% of HIS(NEG)/PCR(NEG) patients developed recurrence, significantly less than those in either HIS(POS) group (P<0.0001). Recurrence in the HIS(NEG)/PCR(POS)/CN(NEG) group (7.7%) was comparable to that in HIS(NEG)/PCR(NEG) patients and significantly lower than that in either HIS(POS) group (P<0.0001). The only independent prognostic factors identified by multivariate analysis were the Breslow thickness of the primary tumour and histopathologic positivity of sentinel nodes. Our findings support previous observations that histopathologic evidence of metastatic melanoma in sentinel lymph nodes is an independent predictor of disease recurrence. In contrast, detection of tyrosinase mRNA by RT-PCR alone does not appear to increase the likelihood of short-term disease recurrence.Modern Pathology 04/2007; 20(4):427-34. DOI:10.1038/modpathol.3800754 · 6.36 Impact Factor
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ABSTRACT: Although the incidence of melanoma is still rising in Caucasian populations, the increase in mortality has leveled off. Improvements in early diagnosis, with more frequent diagnosis of low-risk patients (i.e. those with <1 mm of tumor thickness), is the main reason for these divergent developments. Primary prevention has not yet been successful and recent studies have demonstrated the lack of effectiveness of sunscreen in preventing nevi in children. Progress was made in early melanoma diagnosis when dermoscopy and digital dermoscopy were introduced, and computer algorithms have proved to be highly efficacious for automated melanoma diagnosis. Primary melanomas are now excised with narrower surgical margins of 1-2 cm. Sentinel-node biopsy is recommended as a nodal staging procedure in patients with tumor thickness of 1 mm and more, but the prognostic impact of this procedure has not yet been demonstrated. New imaging techniques, e.g. whole-body MRI and PET-CT, provide more accurate staging, particularly in patients with apparent metastasis, and facilitate decisions on surgical treatment strategies. Staging is now based on the 2001 TNM classification including tumor thickness and histopathologic ulceration in stages I and II and lymph node micro and macro-metastasis in stage III. A stage- and risk-adopted follow-up schedule is proposed for melanoma surveillance. Adjuvant therapy with interferon-alpha in high-risk patients offers a small benefit in terms of recurrence-free and overall survival; the optimal dosage and duration of this treatment are still to be defined. Almost no progress has been made in the medical treatment of disseminated metastasis of melanoma. Therapy with dacarbazine and a few other single agents remains the first-line treatment approach of choice. A number of new treatment modalities, including targeted molecules and immunologic approaches with monoclonal antibodies, are under development; hopefully, new treatment modalities will be available in the near future.Melanoma Research 05/2007; 17(2):117-27. DOI:10.1097/CMR.0b013e328042bb36 · 2.10 Impact Factor