Diagnostic and prognostic implications of the unfolding molecular biology of bone and soft tissue tumours.
(41/2226)
Sarcomas account for approximately 1-2% of human malignant disease and are relatively uncommon. Histopathological study of these mesenchymal tumours at light microscopic and ultrastructural level may not always provide an unambiguous diagnosis. It has become apparent with the identification of increasing numbers of tumour specific genetic alterations that (cyto) genetic evaluation could become a very helpful adjunct to histopathological assessment in reaching a correct diagnosis. Thus, once the different tumour types can be accurately identified and classified, more meaningful clinical trials can be initiated to evaluate and select optimal methods of management. In addition, an increasing awareness and understanding of the molecular changes associated with, and the genetic variability in, the various tumour groups is beginning to provide important new information about clinical progression and prognosis. (+info)
Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.
(42/2226)
The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast. (+info)
Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.
(43/2226)
OBJECTIVE: To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively. SUMMARY BACKGROUND DATA: A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven. METHODS: Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival. RESULTS: Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver. CONCLUSIONS: GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST. (+info)
Hepatic resection of noncolorectal nonneuroendocrine metastases.
(44/2226)
Because hepatic resection is generally a safe procedure, the indications for resection of noncolorectal nonneuroendocrine (NCNNE) hepatic metastases have broadened. The prognostic features of NCNNE metastases treated surgically were reviewed to define better the value of resection. A retrospective review of patients undergoing liver resection for NCNNE metastases between 1978 and 1998 was undertaken. Thirty-seven patients were identified. Mean age was 56 years, with a median follow-up of 22 months. Primary tumor sites were grouped into gastrointestinal (GI) adenocarcinoma (small bowel, n = 4; pancreas, n = 2; esophagus, n = 1) and other (renal cell, n = 7; sarcoma, n = 7; melanoma, n = 5; adrenal, n = 3; unknown adenocarcinoma, n = 3; thyroid, n = 2; testicular, n = 1; ovarian, n = 1; breast, n = 1). All patients underwent surgery for cure. Metastases were synchronous in 14 patients. There was no surgical mortality. Overall 5-year survival rate was 45%. Five-year survival rates were better for patients with non-GI-origin metastases (60% v 0%; P =.01). Long-term survival was seen only in patients with non-GI-origin metastases. The extent of resection, presence of synchronous metastases, or disease-free interval from time of original disease to presentation with liver metastases were not predictive of outcome. We conclude that patients with NCNNE hepatic metastases can undergo liver resection with an expectation of prolonged survival. However, patients with liver metastases from GI primary tumors other than the colorectum are unlikely to show extended survival. (+info)
Induction of skin papillomas, carcinomas, and sarcomas in mice in which the connexin 43 gene is heterologously deleted.
(45/2226)
It has been suggested that blocked gap junctional intercellular communication plays a crucial part in multistage carcinogenesis. The mouse skin tumor-promoting phorbol esters are potent inhibitors of gap junctional intercellular communication and this inhibition is considered to be a mechanism by which clonal expansion of "initiated" cells is promoted. We examined whether mice in which the gene for a gap junction protein, connexin 43, is heterozygously deleted are more susceptible to chemical carcinogenesis; connexin 43 is expressed in the basal cell layer and the dermis of the skin. When the back skin was painted with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol 13-acetate, the incidence and yields of both papillomas and carcinomas were similar in connexin 43+/- and connexin 43+/+ mice; for this experiment, the original mice with C57BL/6 genetic background was crossed with CD1 strain for three generations. Subcutaneous injection of 7, 12-dimethylbenz[a]anthracene resulted in induction of fibrosarcomas in connexin 43+/- and connexin 43+/+ mice to a similar extent. All papillomas and carcinomas induced with 7, 12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol 13-acetate contained the 7,12-dimethylbenz[a] anthracene-specific mutation in the ras gene (A to T transversion at the 61st codon). About 50% of fibrosarcomas also contained this mutation, but in the Ki-ras gene; there was no difference in the prevalence of this mutation in tumors from connexin 43+/- and connexin 43+/+ mice. None of the tumors examined, however, showed any mutation in the connexin 43 gene. These results suggest that the deletion of one allele of the connexin 43 gene does not significantly contribute to, nor alter, the molecular events involved in skin carcinogenesis. These results are compatible with previous observations that nongenetic disruption of function rather than mutations of connexins, commonly occurs in cancer cells. (+info)
Prosthetic reconstruction of the femur for primary bone sarcoma.
(46/2226)
The survival of patients and implants, complications and functional outcome were reviewed in 25 consecutive femoral endoprosthetic reconstructions for treatment of primary bone sarcoma. The diagnosis was chondrosarcoma in 11, osteosarcoma in 10, MFH in 3 and Ewing's tumour in 1. Median follow up was 64 months (34 to 219) and median age at operation was 29 years (10 to 70). Twelve remained disease free at review. One had amputation for local recurrence and another was alive with metastases. 11 patients died at a median of 13 months (5 to 128); 8 from metastatic disease and 3 from other causes. Four implants were revised, at a median of 95 months (53 to 136); two for fractures of the stem and two for aseptic loosening. Three implants had radiological evidence of loosening at a median of 43 months (34 to 49). Fourteen patients had significant complications. The median functional score using the Musculoskeletal Tumour Society system was 68%. In our experience, prosthetic reconstruction of the femur does not compromise survival, although there is a significant complication rate. (+info)
Platelet and coagulation activation with vascular endothelial growth factor generation in soft tissue sarcomas.
(47/2226)
Angiogenesis and activated blood coagulation are involved in tumor growth and metastasis. Although some have suggested that activation of coagulation in tumors is not linked to activation of platelets, no data exist to either support or refute this concept. However, platelet turnover in cancer patients is often increased, and platelets are carriers of angiogenic growth factors. We hypothesized that platelets are involved in tumor-associated angiogenesis. To obtain evidence supporting this hypothesis, we have studied whether the angiogenic and coagulation pathways and platelets are concomitantly activated in cancer patients with soft tissue sarcomas (STSs) using a novel method to detect activated platelets in tumor specimens. Twelve patients with STS were selected on the basis of having intratumoral accumulation of fluid, which was aspirated. These accumulations demonstrated very high concentrations of vascular endothelial growth factor and coagulation factors (including thrombin-antithrombin-complex). Tumor specimens showed dense vascularization with intense vascular endothelial growth factor expression and the presence of activated platelets. Taken together, these results support the concept that angiogenesis, blood coagulation, and platelets are concomitantly activated in STS and support the hypothesis that platelets contribute to tumor-induced angiogenesis. (+info)
Clinical value of [18-F]] fluorodeoxyglucose positron emission tomography imaging in soft tissue sarcomas.
(48/2226)
OBJECTIVE: To evaluate positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) for clinical application in soft tissue sarcomas. SUMMARY AND BACKGROUND DATA: FDG PET is a promising noninvasive method for the preoperative assessment of soft tissue sarcomas and may complement radiologic tomography. METHODS: Data from 50 consecutive patients with 59 masses, either suspicious for primary or locally recurrent soft tissue sarcoma, were prospectively gathered. The semiquantitative FDG uptake (standardized uptake values [SUVs]) was calculated in tumor and normal tissue (muscle). Histopathology of surgical specimens and follow-up data were used as control criteria. RESULTS: In primary soft tissue sarcomas, PET displayed a sensitivity of 91% and a specificity of 88%. Local recurrence was detected with a sensitivity of 88% and a specificity of 92%. All intermediate-grade and high-grade soft tissue sarcomas (primary and locally recurrent) were visualized with a precise differentiation from muscle. Fifty percent of the low-grade sarcomas showed an FDG uptake equivalent to muscle (false-negative results in one primary and three recurrent soft tissue sarcomas). Benign soft tissue tumors (e.g., lipoma, leiomyoma, ganglion) did not accumulate FDG. Inflammation resulted in an increased FDG uptake. The semiquantitative FDG uptake (SUVs) correlated with tumor grade but not with size and histologic type. CONCLUSION: High-grade and intermediate-grade soft tissue sarcomas are amenable to PET imaging, whereas low-grade lesions may not be depicted. SUVs for FDG correlate with tumor grade in soft tissue sarcomas. Benign soft tissue tumors are differentiated from higher-grade soft tissue sarcomas. These data show that FDG-PET can complement preoperative radiologic assessment for soft tissue sarcomas and that FDG-PET is a powerful diagnostic tool for detecting high-grade and intermediate-grade local recurrence. (+info)