Association of positive transection margins with gastric cancer survival and local recurrence.

PURPOSE: To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent. METHODS: Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared. RESULTS: Among 2384 patients undergoing curative intent resection, 108 (4.5 %) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1-2 disease but was not in patients with >3 positive nodes or T3-4 disease. Local recurrence occurred in 16 % of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins. CONCLUSIONS: Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.

Malignant progression in IPMN: a cohort analysis of patients initially selected for resection or observation.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) may represent a field defect of pancreatic ductal instability. The relative risk of carcinoma in regions remote from the radiographically identified cyst remains poorly defined. This study describes the natural history of IPMN in patients initially selected for resection or surveillance. METHODS: Patients with IPMN submitted to resection or radiographic surveillance were identified from a prospectively maintained database. Comparisons were made between these two groups. RESULTS: From 1995 to 2010, a total of 356 of 1,425 patients evaluated for pancreatic cysts fulfilled inclusion criteria. Median follow-up for the entire cohort was 36 months. Initial resection was selected for 186 patients (52 %); 114 had noninvasive lesions and 72 had invasive disease. A total of 170 patients underwent initial nonoperative management. Median follow-up for this surveillance group was 40 months. Ninety-seven patients (57 % of those under surveillance) ultimately underwent resection, with noninvasive disease in 79 patients and invasive disease in 18. Five of the 18 (28 %) invasive lesions developed in a region remote from the monitored lesion. Ninety invasive carcinomas were identified in the entire population (25 %), ten of which developed the invasive lesion separate from the index cyst, representing 11 % with invasive disease. CONCLUSIONS: Invasive disease was identified in 39 % of patients with IPMN selected for initial resection and 11 % of patients selected for initial surveillance. Ten patients developed carcinoma in a region separate from the radiographically identified IPMN, representing 2.8 % of the study population. Diagnostic, operative, and surveillance strategies for IPMN should consider risk not only to the index cyst but also to the entire gland.

Preoperative chemotherapy does not influence the number of evaluable lymph nodes in resected gastric cancer.

BACKGROUND: While it is suggested that more than 15 lymph nodes (LNs) should be evaluated for accurate staging of gastric cancer, LN yield in western countries is generally low. The effect of preoperative chemotherapy on LN yield in gastric cancer is unknown. The aim of the present study is to determine whether preoperative chemotherapy is associated with any difference in the number of LNs obtained from specimens of patients who underwent curative surgery for gastric adenocarcinoma. PATIENTS AND METHODS: In 1205 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 1220 patients from the Netherlands Cancer Registry (NCR) who underwent a gastrectomy with curative intent for gastric adenocarcinoma without receiving preoperative radiotherapy, LN yield was analyzed, comparing patients who received preoperative chemotherapy and patients who received no preoperative therapy. RESULTS: Of the 2425 patients who underwent a gastrectomy, 14% received preoperative chemotherapy. Median LN yields were 23 at MSKCC and 10 in the NCR. Despite this twofold difference in LN yield between the two populations, with multivariate Poisson regression, chemotherapy was not associated with LN yield of either population. Variables associated with increased LN yield were institution, female sex, lower age, total (versus distal) gastrectomy and increasing T-stage. CONCLUSIONS: In this patient series, treatment at MSKCC, female sex, lower age, total gastrectomy and increasing primary tumor stage were associated with a higher number of evaluated LNs. Preoperative chemotherapy was not associated with a decrease in LN yield. Evaluating more than 15 LNs after gastrectomy is feasible, with or without preoperative chemotherapy.

Downstaging in pancreatic cancer: a matched analysis of patients resected following systemic treatment of initially locally unresectable disease.

BACKGROUND: Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10-14 months. The objective of this study was to evaluate outcome of initially unresectable patients who respond to multimodality therapy and undergo resection. METHODS: Using a prospectively collected database, patients were identified who were initially unresectable because of vascular invasion and had sufficient response to nonoperative treatment to undergo resection. Overall survival (OS) was compared with a matched group of patients who were initially resectable. Case matching was performed using a previously validated pancreatic cancer nomogram. RESULTS: A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with either systemic therapy or chemoradiation. Initial unresectability was determined by operative exploration (n = 15, 42%) or by cross-sectional imaging (n = 21, 58%). Resection consisted of pancreaticoduodenectomy (n = 31, 86%), distal pancreatectomy (n = 4, 11%), and total pancreatectomy (n = 1, 3%). Pathology revealed T3 lesions in 26 patients (73%), node positivity in 6 patients (16%), and a negative margin in 30 patients (83%). The median OS in this series was 25 months from resection and 30 months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and those who presented with resectable disease (P = .35). CONCLUSIONS: In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced survival similar to those who were initially resectable. Resection is indicated in this highly select group of patients.

Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma.

BACKGROUND: To characterise recurrence patterns and survival following pathologic complete response (pCR) in patients who received preoperative therapy for localised gastric or gastrooesophageal junction (GEJ) adenocarcinoma. METHODS: A retrospective review of a prospective database identified patients with pCR after preoperative chemotherapy for gastric or preoperative chemoradiation for GEJ (Siewert II/III) adenocarcinoma. Recurrence patterns, overall survival, recurrence-free survival, and disease-specific survival were analysed. RESULTS: From 1985 to 2009, 714 patients received preoperative therapy for localised gastric/GEJ adenocarcinoma, and 609 (85%) underwent a subsequent R0 resection. There were 60 patients (8.4%) with a pCR. Median follow-up was 46 months. Recurrence at 5 years was significantly lower for pCR vs non-pCR patients (27% and 51%, respectively, P=0.01). The probability of recurrence for patients with pCR was similar to non-pCR patients with pathologic stage I or II disease. Although the overall pattern of local/regional (LR) vs distant recurrence was comparable (43% LR vs 57% distant) between pCR and non-pCR groups, there was a significantly higher incidence of central nervous system (CNS) first recurrences in pCR patients (36 vs 4%, P=0.01). CONCLUSION: Patients with gastric or GEJ adenocarcinoma who achieve a pCR following preoperative therapy still have a significant risk of recurrence and cancer-specific death following resection. One third of the recurrences in the pCR group were symptomatic CNS recurrences. Increased awareness of the risk of CNS metastases and selective brain imaging in patients who achieve a pCR following preoperative therapy for gastric/GEJ adenocarcinoma is warranted.

The prognostic impact of isolated tumor cells in lymph nodes of T2N0 gastric cancer: comparison of American and Japanese gastric cancer patients.

BACKGROUND: The clinical significance of immunohistochemically detected isolated tumor cells (ITC) in lymph nodes of gastric cancer patients is controversial. This study examined the prognostic impact of ITC on patients with early-stage gastric cancer in two large volume centers in the United States and Japan. METHODS: Fifty-seven patients with T2N0M0 gastric carcinoma who underwent gastric resection between January 1987 and January 1997 at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and 107 patients resected at National Cancer Center Hospital (NCCH) in Tokyo between January 1984 and December 1990 were studied. The sections were newly prepared from each lymph node for immunohistochemical staining for cytokeratin. Lymph nodes and original specimens from MSKCC were examined by pathologists in NCCH. The prognostic significance of the presence of ITC in lymph nodes was investigated in patients of both institutions. RESULTS: ITC were identified in 30 of 57 patients (52.6%) at MSKCC and in 38 of 107 patients (35.5%) at NCCH. In both institutions, there was no significant difference in the prognosis of the studied patients with or without ITC (P= .22, .86 respectively). CONCLUSIONS: The presence of ITC detected by immunohistochemistry in the regional lymph nodes did not affect the prognosis of American and Japanese patients with T2N0M0 gastric carcinoma who underwent gastrectomy with D2 lymph node dissection.

Validation of a prognostic nomogram in patients undergoing resection for pancreatic ductal adenocarcinoma in a UK tertiary referral centre.

INTRODUCTION: Survival following resection for pancreatic ductal adenocarcinoma (PDAC) remains poor. The aim of this study was to validate a survival nomogram designed at the Memorial Sloan-Kettering Cancer Centre (MSKCC) in a UK tertiary referral centre. METHODS: Patients who underwent resection for PDAC between 1995 and 2005 were analysed retrospectively. Standard prognostic factors and nomogram-specific data were collected. Continuous data are presented as median (inter-quartile range). RESULTS: Sixty-three patients were analysed. The median survival was 326 (209-680) days. On univariate analysis lymph node status (node +ve 297 (194-471) days versus node -ve 367 (308-1060) days, p=0.005) and posterior margin involvement (margin +ve 210 (146-443) days versus margin -ve 355 (265-835) days, p=0.024) were predictors of a poor survival. Only lymph node positivity was significant on multivariate analysis (p=0.006). The median nomogram score was 217 (198-236). A nomogram score of 113-217 predicted a median survival of 367 (295-847) days compared to 265 (157-443) days for a score of 218-269, p=0.012. CONCLUSION: Increasing nomogram score was associated with poorer survival. However the accuracy demonstrated by MSKCC could not be replicated in the current cohort of patients and may reflect differences in patient demographics, accuracy of pathological staging and differences in treatment regimens between the two centres.

Current management of cystic neoplasms of the pancreas.

Over the last decade there has been a dramatic increase in the number of patients identified with pancreatic cysts. This increase has been largely attributed to advances in imaging. The majority of these cysts represent benign neoplasms; however, a significant fraction of these are pre-malignant or malignant. Because the majority of these neoplasms are benign, many reports have advocated a selective approach to surgical resection. Here we review the literature that has contributed to the development of our approach to the management of these cystic neoplasms. We provide an overview of the key features in diagnosis and in predicting malignancy. Particular attention is given to the natural history and management of intraductal papillary mucinous neoplasms (IPMN).

Effect of blood transfusion on outcome after pancreaticoduodenectomy for exocrine tumour of the pancreas.

BACKGROUND: Blood transfusion is thought to have an immunosuppressive effect. The aims of this study were to examine survival in patients with pancreatic cancer receiving blood transfusion in association with pancreaticoduodenectomy, and to define preoperative risk factors for subsequent transfusion. METHODS: A retrospective review was performed of a prospective database of patients with exocrine tumours of the head of the pancreas who had undergone pancreaticoduodenectomy between 1998 and 2003. Clinical data, transfusion records and preoperative laboratory values were recorded. RESULTS: A total of 294 patients underwent pancreaticoduodenectomy for exocrine tumours in the pancreatic head. Of these, 140 (47.6 per cent) received a blood transfusion. Their median survival was 18 months, compared with 24 months for those who did not have a transfusion (P = 0.036). Postoperative transfusion, margin status and node stage were independent predictors of survival. Age and preoperative total bilirubin and haemoglobin levels were the only preoperative factors that correlated with transfusion. CONCLUSION: In patients with exocrine tumours of the pancreas, blood transfusion should be avoided when possible. Preoperative risk factors can identify patients who are likely to require transfusion and would therefore benefit most from blood conservation methods.

A phase II trial of neoadjuvant cisplatin-fluorouracil followed by postoperative intraperitoneal floxuridine-leucovorin in patients with locally advanced gastric cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy with intravenous (i.v.) cisplatin and fluorouracil (5-FU), surgery and postoperative intraperitoneal (i.p.) floxuridine (FUdR) and leucovorin (LV) in patients with locally advanced gastric cancer. PATIENTS AND METHODS: Preoperative staging was confirmed by laparoscopy (LAP). Two cycles of i.v. cisplatin (20 mg/m(2)/day, rapid infusion) and 5-FU (1000 mg/m(2), continuous 24-h infusion), given on days 1-5 and 29-34, were followed by a radical gastrectomy and a D2 lymphadenectomy. Patients having R0 resections were to receive three cycles of i.p. FUdR (1000 mg/m(2)) and LV (240 mg/m(2)), given on days 1-3, 15-17 and 29-31. Intraperitoneal chemotherapy was begun 5-10 days from surgery. RESULTS: Thirty-eight patients were treated. Both preoperative and postoperative chemotherapy were well tolerated. T stage downstaging (pretreatment LAP versus surgical pathological stage) was seen in 23% of patients. The R0 resection rate was 84%. Neither an increase in postoperative morbidity nor operative mortality was noted. With a median follow-up of 43.0 months, 15 patients (39.5%) are still alive (median survival 30.3 months). Good pathologic response, seen in five patients (15%), was associated with better survival (P = 0.053). Peritoneal and hepatic failures were found in 22% and 9% of patients, respectively. Quality of life seemed to be preserved. CONCLUSIONS: Neoadjuvant cisplatin/5-FU followed by postoperative i.p. FUdR/LV can be safely delivered to patients undergoing radical gastrectomy and D2 lymphadenectomy. The R0 resection and the survival rates are encouraging. An association between pathologic response and patient outcome was suggested.

Altered patterns of RB expression define groups of soft tissue sarcoma patients with distinct biological and clinical behavior.

BACKGROUND: Function of the retinoblastoma tumor suppressor protein (pRB) may be compromised at a genetic level by gene loss or mutation or at a post-translational level by hyperphosphorylation. In this study, we examined adult soft tissue sarcomas (ASTS) to determine if alterations of pRB were associated with distinct patterns of pRB expression and clinical outcome. DESIGN: We investigated 86 ASTS patients using monoclonal antibodies that distinguish between hyperphosphorylated and underphosphorylated pRB products. We also used microsatellite analysis to investigate the genetic status of the RB locus. We correlated pRB alterations with proliferative activity, and with clinicopathological outcomes. RESULTS: Altered patterns of pRB expression are common in ASTS occurring in 84% of cases, and it is significantly associated with proliferative activity (p<0.001). Patients whose tumors either lack expression of pRB, or express hyperphosphorylated forms of pRB, have poor survivals compared to patients whose tumors exhibit a normal, underphosphorylated pattern of pRB expression (p=0.03). In addition, 63% of cases lacking expression of pRB showed loss-of-heterozygosity at the locus. CONCLUSIONS: Inactivation of pRB is common in adult STS, which may be due to either gene loss or post-translational modification, namely hyper-phosphorylation. Both mechanisms are associated with tumor cell proliferation and poor survival.

Soft tissue sarcoma: advances in understanding and management.

Soft tissue sarcomas are a rare group of neoplasms readily dispersed throughout the body with different histopathologies and different outcomes. The present review summarizes advances made in biology, distribution and natural history, and emphasises predictive models for outcome. Complete resection remains the major factor in providing cure, with limited benefits in the control of the local disease by radiation therapy and only minimal benefit of systemic therapy for metastatic disease. Identification of targeted therapy utilising direct specific molecular targets raises hope that future progress in control, if not cure, is realistic.

[Therapeutic management of intra-abdominal and retroperitoneal soft tissue sarcomas]. / Therapeutisches Management intraabdomineller und retroperitonealer Weichgewebssarkome.

In this article, we review the diagnostics, therapy, follow-up, and prognosis of intra-abdominal and retroperitoneal soft tissue sarcomas. There are descriptions and discussion of the surgical techniques, advantages and disadvantages of various types and combinations of adjuvant and neoadjuvant therapies, therapy in case of nonresectability, and procedures for desmoid tumors. Further, treatment results, control methods, and studies on new therapeutic approaches are presented.

Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma.

BACKGROUND: The purpose of this study was to retrospectively analyze the relationship between neo-adjuvant chemotherapy (NAC) and outcome in patients with high-grade extremity sarcomas. PATIENTS AND METHODS: Inclusion criteria were high-grade, deep, >5 cm extremity soft tissue sarcomas. Patients diagnosed between 1990 and 2001 were treated with surgery only (n=282) or NAC containing doxorubicin/ifosfamide/mesna (AIM) (n=74). The stratified Cox proportional hazards model was used to test the effect of NAC on disease-specific survival and recurrence while adjusting for known prognostic factors. RESULTS: NAC was associated with improved disease-specific survival for this cohort of patients (P=0.02). This overall improvement appears to be driven by the benefit of NAC on disease-specific survival for patient with tumors >10 cm. The 3-year disease-specific survival for tumors >10 cm was 0.62 (95% CI: 0.53-0.71) for patients not receiving NAC and 0.83 (95% CI: 0.72-0.95) for patients receiving NAC. CONCLUSION: NAC with AIM was associated with a significant improvement in disease-specific survival in patients with high-grade extremity soft tissue sarcomas >10 cm. These data emphasize the need for further prospective clinical studies of neo-adjuvant or adjuvant chemotherapy for patients with large high-grade extremity sarcomas.

Circulating angiogenic factor levels correlate with extent of disease and risk of recurrence in patients with soft tissue sarcoma.

BACKGROUND: Tumor angiogenesis, or new blood vessel formation, is regulated by a balance between pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and anti-angiogenic factors such as endostatin. PATIENTS AND METHODS: To investigate this angiogenic balance in soft tissue sarcomas (STS), blood samples were collected from 76 STS patients and 15 healthy controls, and analyzed for VEGF, bFGF and endostatin using quantitative enzyme-linked immunosorbent assays (ELISA). RESULTS: Forty-one patients (54%) had primary tumors, 20 (26%) had local recurrences and 15 (20%) had metastatic disease with or without local disease. Levels of all three angiogenic factors were highly variable in STS patients. Mean levels of VEGF and bFGF were 12 and 14 times higher, respectively, in patients compared with controls (P<0.0001). VEGF levels correlated with size of tumor, with the highest levels found in tumors >10 cm in size. Patients with metastases had endostatin levels 45% lower than patients without metastases (P=0.047). In 54 patients who underwent resection of primary disease or local recurrence, low pre-operative bFGF level was associated with a higher risk of subsequent recurrence (P=0.044). CONCLUSIONS: STS secrete widely variable levels of angiogenic factors, and levels of specific factors may correlate with extent of disease, predict risk of recurrence and possibly guide the use of anti-angiogenic agents.

Resection of the sciatic, peroneal, or tibial nerves: assessment of functional status.

BACKGROUND: Lower-extremity tumors are often treated by amputation rather than limb-sparing excision that sacrifices the sciatic nerve or a branch. This study assessed the functional outcome of major nerve sacrifice during limb-sparing resections for lower-extremity soft tissue sarcoma. METHODS: Patients who underwent division of the sciatic, tibial, or peroneal nerve(s) during limb-sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven surviving patients evaluated their pre- and postoperative functional status by self-administered questionnaire (six sciatic, two tibial, and three peroneal nerve divisions). RESULTS: Eighteen patients (10 male, 8 female; 14-84 years old) had nine primary and nine locally recurrent tumors. Tumors were high (16) or low grade (two). Five patients died of disease and two died of other causes. Median overall survival was 50 months. One of 11 reported increased pain. Eight had new phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All patients used an ankle brace to walk after a sciatic (four) or peroneal (one) division. Walking ability and distance after surgery was unchanged (nine), improved (one), and worsened (one). Standing improved in 7 of 11 patients. Proprioception in the affected extremity was retained in six. The median postoperative leg functional score was 8 (1 = worst; 10 = best). No patient developed foot ulcers. One patient underwent amputation for recurrence. All patients preferred their status over having an amputation. CONCLUSIONS: Objectively and subjectively, division of the major lower-extremity nerves causes acceptable functional deficits in most patients. Resection of affected sciatic nerve (branches) during limb-sparing tumor surgery is an excellent alternative to amputation.

Reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1.

BACKGROUND: Patients with multiple endocrine neoplasia type 1 and hyperparathyroidism often undergo multiple operations because of inadequate initial surgery, presence of supernumerary and ectopic glands, regrowth of remnant glands, or autograft hyperfunction. Management of this patient population is complex. METHODS: From January 1975 to December 2000 we performed 94 reoperative parathyroidectomies consisting of 79 neck reexplorations, 12 autograft removals, and 3 median sternotomies in 75 patients. Data were gathered by retrospective chart review and follow-up telephone interviews. RESULTS: Excluding autograft excision, reoperative surgery was successful (normocalcemia longer than 6 months) in 91%; autograft removal was successful in only 58%. With a median follow-up of 59 months, 64% of patients are currently free from hypercalcemia, and this outcome was not influenced by the total number of glands resected. The median time to recurrent hypercalcemia was 125 months. Thirty patients received an autograft after reoperation. The complication rate for all reoperations was 12%, including permanent recurrent laryngeal nerve injury in 2 patients (2.1%). CONCLUSIONS: Reoperative parathyroidectomy in patients with multiple endocrine neoplasia type 1 was safe and successful in the majority of patients; however, recurrent hyperparathyroidism is likely to develop in most individuals beyond 10 years of follow-up. The total number of glands accounted for after reoperation is not associated with successful outcome.

Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases.

PURPOSE: A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations. METHODS: We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses. RESULTS: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was <5% in 47 (57%) cases and > or =5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined as > or =10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as > or =5% RC; P < 0.01), presence of necrosis (> or =5% of tumor mass; P < 0.05), and overexpression of P53 (P < 0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P < 0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P < 0.01). CONCLUSION: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (> or =5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.