Biomedical subjects

C L Slingluff

Publications and source records attributed to C L Slingluff.

At least 37 records · Page 2Linked to original sources

PubMed1998

Human melanoma patients recognize an HLA-A1-restricted CTL epitope from tyrosinase containing two cysteine residues: implications for tumor vaccine development.

To identify shared epitopes for melanoma-reactive CTL restricted by MHC molecules other than HLA-A*0201, six human melanoma patient CTL lines expressing HLA-A1 were screened for reactivity against the melanocyte differentiation proteins Pmel-17/gp100, MART-1/Melan-A, and tyrosinase, expressed via recombinant vaccinia virus vectors. CTL from five of the six patients recognized epitopes from tyrosinase, and recognition of HLA-A1+ target cells was strongly correlated with tyrosinase expression. Restriction by HLA-A1 was further demonstrated for two of those tyrosinase-reactive CTL lines. Screening of 119 synthetic tyrosinase peptides with the HLA-A1 binding motif demonstrated that nonamer, decamer, and dodecamer peptides containing the sequence KCDICTDEY (residues 243-251) all reconstituted the CTL epitope in vitro. Epitope reconstitution in vitro required high concentrations of these peptides, which was hypothesized to be a result of spontaneous modification of cysteine residues, interfering with MHC binding. Substitution of serine or alanine for the more N-terminal cysteine prevented modification at that residue and permitted target cell sensitization at peptide concentrations 2 to 3 orders of magnitude lower than that required for the wild-type peptide. Because spontaneous modification of sulfhydryl groups may also occur in vivo, tumor vaccines using this or other cysteine-containing peptides may be improved by amino acid substitutions at cysteine residues.

Alanine↗

PubMed1998

Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha.

DNA-based immunization strategies designed to elicit cellular antitumor immunity offer an attractive alternative to protein- or peptide-based approaches. In the present study we have evaluated the feasibility of DNA vaccination for the induction of CTL reactivity to five different melanoma Ags in vitro. Cultured, monocyte-derived dendritic cells (DC) were transiently transfected with plasmid DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3 by particle bombardment and used to stimulate autologous PBMC responder T cells. CTL reactivity to these previously identified melanoma Ags was reproducibly generated after two or three stimulations with genetically modified DC. Co-ordinate transfection of two melanoma Ag cDNAs into DC promoted CTL responders capable of recognizing epitopes from both gene products. Coinsertion of genes encoding the Th1-biasing cytokines IL-12 or IFN-alpha consistently enhanced the magnitude of the resulting Ag-specific CTL reactivity. Importantly, DC transfected with a single melanoma Ag cDNA were capable of stimulating Ag-specific CTL reactivity restricted by multiple host MHC alleles, some of which had not been previously identified. These results support the inherent strengths of gene-based vaccine approaches that do not require prior knowledge of responder MHC haplotypes or of relevant MHC-restricted peptide epitopes. Given previous observations of in situ tumor HLA allele-loss variants, DC gene vaccine strategies may elicit a greater diversity of host therapeutic immunity, thereby enhancing the clinical utility and success of such approaches.

Antigens, Neoplasm↗

PubMed1998

The class I antigen-processing pathway for the membrane protein tyrosinase involves translation in the endoplasmic reticulum and processing in the cytosol.

Formation of major histocompatibility complex class I-associated peptides from membrane proteins has not been thoroughly investigated. We examined the processing of an HLA-A*0201-associated epitope, YMDGTMSQV, that is derived from the membrane protein tyrosinase by posttranslational conversion of the sequence YMNGTMSQV. Only YMDGTMSQV and not YMNGTMSQV was presented by HLA-A*0201 on cells expressing full-length tyrosinase, although both peptides have similar affinities for HLA-A*0201 and are transported by TAP. In contrast, translation of YMNGTMSQV in the cytosol, as a minigene or a larger fragment of tyrosinase, led to the presentation of the unconverted YMNGTMSQV. This was not due to overexpression leading to saturation of the processing/conversion machinery, since presentation of the converted peptide, YMDGTMSQV, was low or undetectable. Thus, presentation of unconverted peptide was associated with translation in the cytosol, suggesting that processing of the full-length tyrosinase occurs after translation in the endoplasmic reticulum. Nevertheless, presentation of YMDGTMSQV in cells expressing full-length tyrosinase was TAP (transporter associated with antigen processing) and proteasome dependent. After inhibition of proteasome activity, tyrosinase species could be detected in the cytosol. We propose that processing of tyrosinase involves translation in the endoplasmic reticulum, export of full-length tyrosinase to the cytosol, and retransport of converted peptides by TAP for association with HLA-A*0201.

Amino Acid Sequence↗

PubMed1998

Complete spontaneous regression of pulmonary metastatic melanoma.

BACKGROUND: Complete spontaneous regression of melanoma metastatic to the lungs is a rare event. OBJECTIVE: To report a case of biopsy-proven melanoma metastatic to the lung with complete spontaneous regression. METHODS: Multidisciplinary case report. RESULTS: A 35-year-old white female was diagnosed with metastatic melanoma to the lung. A pleural biopsy confirmed the diagnosis. Partial spontaneous regression was noted by a staging computed tomography scan prior to enrollment in an investigational protocol. Complete spontaneous regression occurred over 5 months without any form of conventional or alternative therapy, and the patient remains disease-free 3 years after diagnosis. CONCLUSIONS: Our case represents the seventh case of complete spontaneous regression of melanoma metastatic to the lung, and the only case with histologic confirmation of both the primary and pulmonary metastatic lesions. The patient was pregnant twice between the time of her initial diagnosis of primary melanoma and pulmonary metastatic disease.

Adult↗

PubMed1998

Activated alpha 2-macroglobulin reverses the immunosuppressive activity in human breast cancer cell-conditioned medium by selectively neutralizing transforming growth factor-beta in the presence of interleukin-2.

The immunosuppressive activity of tumor cells may be mediated by tumor-derived cytokines such as transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10). A human breast cancer cell line derived from malignant ascites (BRC 173) secreted TGF-beta, but not IL-10, into tissue culture supernatant (TCS). BRC 173 TCS suppressed natural killer (NK) and lymphokine-activated killer (LAK) cell activity and also blocked the generation of HLA-A*0201-restricted tumor-reactive cytotoxic T-lymphocyte (CTL) lines in vitro. Human alpha 2-macroglobulin (alpha 2M), a plasma protein and cytokine carrier that binds isoforms in the TGF-beta family, was tested for its ability to neutralize the immunosuppressive activity in BRC 173 TCS. alpha 2M was converted to its activated conformation by reaction with methylamine (alpha 2M-MA) and then incubated with normal human peripheral blood lymphocytes (PBL) in the presence of IL-2 and BRC 173 TCS. Lysis of NK targets (K562) and LAK cell targets (DM6 melanoma) by the PBL was examined after 6 days of culture. PBL cultured in IL-2, without TCS or alpha 2M-MA, were lytic for both target cells. BRC 173 TCS substantially suppressed the lytic activity of the PBL in the presence of IL-2. When TGF-beta-neutralizing antibody was added to the PBL culture medium with IL-2 and TCS, a majority of the lytic activity was restored. alpha 2M-MA (280 nM) neutralized almost all of the immunosuppressive activity in the TCS, restoring 80-100% of the lytic activity without any apparent effect on the activity of IL-2. The ability of alpha 2M-MA to counteract immunosuppressive cytokines in breast cancer TCS was evident in serum-containing and serum-free medium. These studies demonstrate the activated alpha 2M can function as a selective cytokine neutralizer to thereby promote the activation of NK, LAK, and tumor-specific CTL responses.

Breast Neoplasms↗

PubMed1997

Association of breast cancer with the finding of atypical ductal hyperplasia at core breast biopsy.

OBJECTIVE: The purpose of the study is to evaluate the prevalence of occult breast carcinoma in surgical breast biopsies performed on nonpalpable breast lesions diagnosed initially as atypical ductal hyperplasia (ADH) by core needle biopsy. BACKGROUND: Atypical ductal hyperplasia is a lesion with significant malignant potential. Some authors note that ADH and ductal carcinoma in situ (DCIS) frequently coexist in the same lesion. The criterion for the diagnosis of DCIS requires involvement of at least two ducts; otherwise, a lesion that is qualitatively consistent with DCIS but quantitatively insufficient is described as atypical ductal hyperplasia. Thus, the finding of ADH in a core needle breast biopsy specimen actually may represent a sample of a true in situ carcinoma. METHODS: Between May 3, 1994, and June 12, 1996, image-guided core biopsies of 510 mammographically identified lesions were performed using a 14-gauge automated device with an average of 7.5 cores obtained per lesion. Atypical ductal hyperplasia was found in 23 (4.5%) of 510 lesions, and surgical excision subsequently was performed in 21 of these cases. In these 21 cases, histopathologic results from core needle and surgical biopsies were reviewed and correlated. RESULTS: Histopathologic study of the 21 surgically excised lesions having ADH in their core needle specimens showed seven (33.3%) with DCIS. CONCLUSIONS: In the authors' patient population, one third of patients with ADH at core biopsy have an occult carcinoma. A core needle breast biopsy finding of ADH for nonpalpable lesions therefore warrants a recommendation for excisional biopsy.

Biopsy, Needle↗

PubMed1996

Shared epitopes for HLA-A3-restricted melanoma-reactive human CTL include a naturally processed epitope from Pmel-17/gp100.

Human CD8+ CTL recognize peptides bound to class I MHC molecules on the surface of melanoma cells. Several peptides derived from melanocyte lineage-specific proteins have been identified as epitopes for HLA-A2 restricted melanoma-reactive CTL. Because less than half of melanoma patients express HLA-A2, it is important to identify CTL epitopes restricted by other common MHC molecules including HLA-A1 and -A3. We have generated HLA-A3-restricted human CTL that recognize one or more shared melanoma Ags. All of the melanomas recognized by one of these CTL lines express Pmel-17/gp100, and those that fail to express this Ag are not lysed. This CTL line also specifically recognizes the lymphoblastoid line C1R-A3 following infection with a recombinant vaccinia encoding the melanocyte lineage-specific protein Pmel-17/gp100. Thus, at least one Pmel-17/ gp100 peptide is an epitope for this CTL line. We have identified ALLAVGATK (Pmel-17/gp100 residues 17-25) as an epitope for this CTL line and have shown that it is naturally processed and presented by HLA-A3 on melanoma cells. A second HLA-A3-restricted melanoma-reactive CTL line recognizes at least one additional shared epitope. These findings suggest that cellular immune responses directed against multiple shared melanoma epitopes exist in the 20 to 25% of melanoma patients who express HLA-A3. In addition, immunotherapy directed against Pmel-17/gp100 and other shared melanoma Ags may be useful in a large subset of these patients.

Amino Acid Sequence↗

PubMed1996

An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins.

T lymphocytes recognize antigens consisting of peptides presented by class I and II major histocompatibility complex (MHC) molecules. The peptides identified so far have been predictable from the amino acid sequences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cells. The peptide results from posttranslational conversion of asparagine to aspartic acid. This change is of central importance for peptide recognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has not been previously described for any MHC-associated peptide and represents the first demonstration of posttranslational modification of a naturally processed class I-associated peptide. This observation is relevant to the identification and prediction of potential peptide antigens. The most likely mechanism for production of this peptide leads to the suggestion that antigenic peptides can be derived from proteins that are translated into the endoplasmic reticulum.

Amino Acid Sequence↗

PubMed1994

Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the lung: epitope reconstitution with peptides extracted from HLA-Aw68.

Cytotoxic T-lymphocytes (CTLs) specific for autologous human squamous cell cancer of the lung were generated by stimulation of peripheral blood lymphocytes with autologous tumor cells in vitro. The CTL line was >97% CD3+, CD8+, CD16- and produced tumor necrosis factor-alpha, gamma-interferon, and granulocyte-macrophage colony-stimulating factor after stimulation with autologous tumor. The CTLs lysed autologous tumor but failed to recognize autologous or histocompatibility leukocyte antigen-matched lymphoid cells, K562, or allogeneic tumor cells of several histological types. Antibody-blocking studies suggested that the CTLs recognized one or more antigens presented by the class I major histocompatibility complex molecule Aw68. To characterize these antigens further, histocompatibility leukocyte antigen Aw68 molecules were extracted from the squamous cell cancer of the lung tumor line by immunoaffinity chromatography, and the associated peptides were eluted in acid and separated by reversed-phase high-performance liquid chromatography. Reconstitution of the CTL epitope was evaluated by adding these peptides to autologous Epstein-Barr virus-transformed B-cells. Two peaks of reconstituting activity were observed, suggesting that these CTLs recognize at least two Aw68-associated peptides. This study confirms the existence of a CTL response against autologous human squamous cell cancer of the lung and suggests that this CTL response is directed against peptide epitopes presented by the class I major histocompatibility complex molecules. It is anticipated that this approach will permit identification of peptide epitopes for lung cancer-specific CTLs.

Carcinoma, Squamous Cell↗

PubMed1994

Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines.

Of several thousand peptides presented by the major histocompatibility molecule HLA-A2.1, at least nine are recognized by melanoma-specific cytotoxic T lymphocytes (CTLs). Tandem mass spectrometry was used to identify and to sequence one of these peptide epitopes. Melanoma-specific CTLs had an exceptionally high affinity for this nine-residue peptide, which reconstituted an epitope for CTL lines from each of five different melanoma patients tested. Recognition by multiple CTL lines suggests that this may be a promising candidate for use in peptide-based melanoma vaccines.

Amino Acid Sequence↗

PubMed1994

Direct analysis of tumor-associated peptide antigens.

Adoptive immunotherapy with tumor-specific cytotoxic T lymphocytes (CTLs) can induce tumor regressions in animals and in human cancer patients. Antigens recognized by CTLs from cancer patients are being sought as possible immunogens, a number of which have been identified during the past year. The ultimate result may be the development of novel peptide-based immunotherapies and a new understanding of the T-cell response to human cancer.

Amino Acid Sequence↗

PubMed1994

Surgical management of regional lymph nodes in patients with melanoma. Experience with 4682 patients.

OBJECTIVE: The purpose of this study was to evaluate a large number of patients with cutaneous melanoma who had or who were at risk for lymph node metastases to contribute to the understanding of the behavior of and appropriate management of draining nodes. A major goal of the study was to reassess the clinical impact of elective lymph node dissections (ELND) in a large patient population. SUMMARY BACKGROUND DATA: Large retrospective studies suggest that ELND may improve the prognosis of patients with intermediate thickness melanomas; however, that improvement has not been observed in two randomized prospective controlled trials. METHODS: The charts of 4682 patients treated at a single institution for localized or regional disease were reviewed individually. The median follow-up was 4.7 years, with 814 patients followed more than 10 years. The data were tabulated and evaluated with the aid of a computer data base system. RESULTS: Among patients with nodal metastases, 10% of nodal metastases were to contralateral nodes, and 6% were to nodal basins that would not be predicted by classic models of lymphatic drainage; in 13% of patients, nodal metastases occurred to greater than one nodal basin (3% of the entire study group). For all thickness ranges, the incidence of nodal metastases was comparable to the incidence of distant metastases; intermediate-thickness lesions had no relative predilection for nodal metastases. At the initial evaluation, regional nodal basins were clinically negative in 3550 patients, of whom 911 (25.7%) underwent ELND. Stratified into five thickness groups (< 0.76 mm, 0.76 to 1.5 mm, 1.5 to 2.5 mm, 2.5 to 4 mm, and > 4 mm), pathologically positive nodes were identified in 0%, 5%, 16%, 24%, and 36%, respectively (16% overall). Among the 911 patients who underwent ELND, 214 (23%) had nodal metastases, 143 at the time of ELND and 71 at a later date. Of these 71 patients, 31 (44%) had nodal metastases in a previously dissected nodal basin, and 40 (56%) had them in basins not previously dissected. The survival of patients with clinically negative nodes treated with and without ELND were compared. The two groups were well matched for major prognostic factors. Stratified by Breslow thickness and primary site, no significant improvement in survival was observed with ELND. CONCLUSIONS: Because of the significant incidence of metastases to contralateral and atypical nodal basins, lymphoscintigraphy may be justified for the preoperative evaluation of patients for ELND. However, the therapeutic value of ELND is questionable as a result of (1) the finding that the risk of nodal metastases is not relatively more common than is that of distant metastases among patients with intermediate-thickness melanomas, (2) the fact that only 16% of ELND were positive, (3) the finding that ELND may not prevent recurrent nodal disease in the dissected basin, and (4) the absence of any apparent impact on survival among patients who underwent ELND.

Female↗

PubMed1993

Recognition of human melanoma cells by HLA-A2.1-restricted cytotoxic T lymphocytes is mediated by at least six shared peptide epitopes.

HLA-A2.1-associated peptides were extracted from human melanoma cell lines and used to study epitopes for melanoma-specific HLA-A2.1-restricted CTL. CTL were generated from tumor-involved nodes by in vitro stimulation, initially with autologous melanoma cells and subsequently with allogeneic A2.1+ melanoma cells. These CTL lysed autologous melanoma plus four allogeneic HLA-A2.1+ melanomas, including an HLA-A2.1-transfected melanoma. K562, HLA-A2- melanomas and HLA-A2+ nonmelanomas were not lysed. HLA-A2.1 molecules were purified from human melanoma cell lines by immunoaffinity column chromatography of detergent-solubilized cell pellets. Peptides bound to the MHC molecules were acid eluted and fractionated by reversed phase HPLC. Individual fractions were assessed for their ability to reconstitute melanoma-specific epitopes by addition to the HLA-A2.1+ Ag-processing mutant, 721.174XCEM.T2 (T2). Five peaks of reconstitution were observed. Second dimension HPLC separations of reconstituting fractions revealed evidence for two distinct reconstituting peptides within one of these peaks. Based on these data, a minimum of six distinct peptides associated with HLA-A2.1 and recognized by melanoma-specific CTL are present on these different melanoma lines. These data document the presence of multiple peptide-defined CTL epitopes that are shared by at least three unrelated human melanoma cell lines.

Cell Line↗

PubMed1993

Multiple primary melanoma: incidence and risk factors in 283 patients.

To identify patients with melanoma at risk for a second primary lesion and to assess the prognostic relevance of multiple primary lesions, 7816 patients treated for malignant melanoma have been reviewed. Two to nine primary lesions were identified in 283 patients (3.6%): two lesions were identified in 82% of these 283 patients, three lesions in 11%, and four lesions in 3%. Sixty-four percent were metachronous. Among patients with melanoma, the 10-year actuarial risk of a second primary lesion was 5%; a third of that risk was expressed within 3 months of the initial diagnosis plus a subsequent risk of 0.38% per year. Risk factors for multiple primary lesions were family history of melanoma, thin primaries, male sex, Celtic complexion, and a history of another cancer. Patients with a family history of melanoma had a 14% risk of a second primary lesion during the first 10 years after diagnosis. By univariate and multivariate analyses, there was no survival disadvantage for patients with multiple primary lesions. After median follow-ups of 3.7 and 4.8 years, respectively, 51.7% and 50.5% of the groups with single and multiple primaries were disease free. Mortality rates were 31% and 25%, respectively. It is appropriate to base therapeutic decisions and prognostic evaluations on the specific risk factors of each individual lesion. Identification of patients at high risk for multiple primary lesions may permit early diagnosis and improved outcomes.

Actuarial Analysis↗

PubMed1992

The annual risk of melanoma progression. Implications for the concept of cure.

BACKGROUND: Melanoma may remain clinically dormant for years, and patients may have distant metastatic disease decades after the initial diagnosis is made. Because of this potential for late recurrence, the concept of "cure" for melanoma is not particularly meaningful. METHODS: To understand better the risks of future disease as a function of time elapsed after diagnosis, the clinical course of melanoma was reviewed in 5838 patients. Using conditional probability methods, the risk of recurrent disease and the risk of death were determined for 1-year and 5-year intervals during the first 15 years of follow-up. RESULTS: The estimated 5-year risk of recurrence declined from 44% at the time of diagnosis to 21% after 6 years. The 5-year risk of mortality decreased from 26% after 1 year to 16% after 9 years. Among patients with recurrent or metastatic disease, the annual risk of mortality was approximately 20% per year for 3 years; thereafter, the risk declined markedly. Among patients with thick primary lesions, the greatest risk was during the first few years after diagnosis, but in patients with thin lesions, the risk was distributed evenly over 15 years and did not decrease with time. CONCLUSIONS: Conditional probability methods permit estimation of future risks to address questions frequently asked by patients with cancer who want to know when they can be considered cured of cancer or when the risk of recurrent disease has decreased. These data on the future risk of recurrent disease and mortality can give a patient meaningful information on which to base life decisions.

Female↗

PubMed1992

Recurrent malignant melanoma: the identification of prognostic factors to predict survival.

The prognostic factors for stage 1, 2 melanoma have been elucidated. Tumor thickness, ulceration of the primary melanoma, and perhaps, primary site may be used to predict the percentage of patients with regional nodal disease or systemic metastases and the prognosis of patients who have only cutaneous disease at diagnosis. Very little is known about prognosis once there is a recurrence. A retrospective, computer-aided chart review identified 4,185 patients registered at the Duke University Melanoma Database who had stage 1, 2 disease at diagnosis. During a mean follow-up period of 7 years, 35.9% experienced a recurrence. Local regional recurrences explained 62.5% to 85.5% of the recurrences. Even after elective node dissections, local regional recurrences explained most relapses (58.1%). Sixty-five percent of the recurrences occurred within the first 3 years of of follow-up. There was a pronounced difference in 5-year survival in those patients who suffered a recurrence sometime during their clinical course compared with those who never relapsed (p = 0.00001, for trunk primary melanoma). Patients with local or regional recurrence have a better prognosis than patients who relapse systemically, with 5-year survivals from the time of recurrence of 55% for a patient with a local recurrence, 51% for a patient with a regional nodal recurrence, and 20% for a patient with a systemic recurrence. A multivariate regression analysis identified thickness, ulceration of the primary melanoma, and age and location of the primary melanoma on the extremity as variables that predicted prognosis. The only factors concerning the recurrent state that added prognostic information was the disease-free interval and the presence of systemic metastases as the initial recurrence.

Adolescent↗

PubMed1992

Isolated limb perfusion for recurrent melanoma of the extremity.

Recent reports in the literature suggest that hyperthermic isolated limb perfusion (HILP) may be effective in preventing local recurrence in patients with deeply invasive melanoma or in patients with recurrent disease confined to the extremity. It has been used in the past as an adjuvant treatment after resection of the primary melanoma or recurrence, or as a therapeutic measure if all the disease on the extremity cannot be resected. A prospective, nonrandomized trial of 16 patients with melanoma with recurrent disease confined to the extremity underwent HILP. The protocol involved the wide local excision of all recurrent disease when possible, elective or therapeutic node dissection when indicated, and HILP using cisplatin. In 11 patients in whom all recurrent disease could be resected and the HILP was considered prophylactic, only 1 patient's disease has recurred in the perfusion circuit. Before the perfusion, the 11 patients had a total of 19 local or intransit recurrences. Of the 5 patients in whom all recurrent disease could not be resected, disease persisted in 4 patients. When compared with a concurrent control population of patients with extremity melanoma who had a local recurrence and were not perfused, the patients with melanoma who underwent HILP had a significant prolongation of disease-free survival (p less than 0.05), but a similar actuarial survival. In this study, we demonstrate that HILP can prevent local regional recurrences in patients with metastatic melanoma who are at high risk for further recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Arm↗

PubMed1992

Anorectal melanoma: clinical characteristics and the role of abdominoperineal resection.

Twenty-four patients with primary anorectal melanoma diagnosed since 1974 have been retrospectively studied. The most common presenting symptom was rectal bleeding, typically misdiagnosed as hemorrhoids. Progressive disease most commonly presented as a large pelvic mass, diffuse bilateral pulmonary nodules, or diffuse liver metastases. Twenty-one patients (88%) died of their disease; none survived more than 6 years. Among the patients who have died of their disease, mean survival was 2.2 years. Among assessable stage I patients initially managed with abdominoperineal resection (APR), 50% developed recurrent local regional disease (mean disease-free interval = 23 months), compared with 100% of those managed with more limited surgery (mean disease-free interval = 16 months). Even after APR, however, distant metastases were common, and there was no prolongation of survival for patients treated with APR. Primary melanoma of the anorectum has a high metastatic potential and carries a grave prognosis. APR appears to have some effect in controlling local and regional disease, but prolongation of survival will depend both on earlier diagnosis and on development of more successful therapeutic approaches.

Academic Medical Centers↗