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Basic fibroblast growth factor (bFGF), a potent angiogenic peptide, is thought to provide a growth advantage to a number of tumors including squamous cancer of the head and neck. The purpose of this study was to demonstrate the in situ expression of bFGF in lesions of the upper aerodigestive tract (UADT) and to correlate that with clinical parameters and known risk factors for carcinoma. On surgical specimens from 52 patients, we used a colorimetric in situ hybridization assay to determine the expression of BFGF mRNA in normal and pathologic conditions commonly seen in squamous mucosa. The extent of reactivity for the bFGF transcript was recorded on a subjective scale from 1+ to 3+, based on the visual intensity of labeling. These findings were subsequently correlated with clinical data. Basic fibroblast growth factor mRNA was detected at low to moderate levels in all sections of normal mucosa, with no distinction between patients with or without squamous cancer. Inflamed mucosa had comparatively strong expression of bFGF mRNA. Among lesions implicated in the stepwise nature of squamous carcinogenesis, we found increases in bFGF expression that were most significant at the level of carcinoma in situ, persisting through the invasive and nodal metastatic stages of the disease (P

Background. Giant cell tumors (GCTs) of the sacrum are a difficult clinical problem. Wide excision (total sacrectomy) is associated with high morbidity and pelvic/ spinal instability. Curettage with or without supplemental radiotherapy is associated with a high recurrence rate. In view of the proven effectiveness of cryosurgery as an adjunct to curettage for extremity GCT, cryosurgery was used for treatment of GCTs of the sacrum. Methods. Seven patients with GCTs of the sacrum were treated at our institution by conservative surgery from 1973 to 1992. Four patients presented with recurrent tumors after failing previous radiation treatment (dose, 5040 cGy). Four patients were treated with curettage with cryosurgery and three with limited excision with cryosurgery. In the latter procedure after limited excision of the caudal (below S2) part of the tumor, the upper sacral segments were treated with curettage and cryosurgery. This spared the important upper sacral roots and maintained the skeletal integrity. Results. At a median follow-up of 12.25 years (range, 2-14.2 years), all patients were disease free. Local recurrence developed in two patients. Both of these underwent repeat curettage and cryosurgery and have since remained disease free. Two patients had positive second look biopsy with microscopic tumor. Both of these were treated with repeat cryosurgery and have remained disease free. Two patient who developed solitary pulmonary metastases, underwent wedge resection and are alive without disease. No patient suffered neurologic deterioration. Conclusion. Conservative surgery (curettage or partial excision) with adjunct of cryosurgery is our preferred technique for the treatment of GCT of the sacrum. Satisfactory local control could be obtained by close observation, second look biopsy and repeat cryosurgery. The chief advantages of this method include preservation of pelvic and spinal continuity, speed and ease of surgical procedure and less potential blood loss. We recommend it over more radical sacrectomy due to low morbidity and less resultant neurologic deficits. Cancer 1994; 74:1253-60. Key words: giant cell tumor, sacrum neoplasm, cryosurgery, radiation, metastasis.

Background. Bone morphogenetic proteins (BMPs) are potent inducers of bone formation. Functional and immunohistochemical studies have identified BMPs in a subset of osteosarcomas. In the present study, the authors extend the analysis of BMP expression to other bone and soft tissue sarcomas. Methods. Monoclonal antibody AbH3b2/17 against human BMP-2 and BMP-4 was used in avidin-biotin-immunoperoxidase assays with frozen sections of bone tumors (71 specimens), soft tissue sarcomas (69 specimens), and normal tissues. Results. Among bone tumors, BMP was detected in osteosarcomas (17 of 29 samples), malignant fibrous histiocytomas (MFHs) (6 of 6), and the spindle cell sarcomatous components of spindle cell (dedifferentiated) chondrosarcomas (4 of 4), but not in conventional chondrosarcomas (0 of 10) or Ewing's sarcomas (0 of 14). Histologic subtypes of osteosarcoma differed for BMP expression, with 8 of 9 fibrohistiocytic, 9 of 13 osteoblastic, and 0 of 5 chondroblastic lesions showing immunostaining. In all BMP-positive bone tumors, immunostaining was localized in the cytoplasm of primitive mesenchymal cells, with little or no staining in tumor matrix and more mature osteoblastic/chondrocytic cells. Among soft tissue sarcomas, MFHs (11 of 12), liposarcomas (5 of 11), leiomyosarcomas (3 of 9), and malignant schwannomas (3 of 8) showed cytoplasmic BMP immunostaining. Synovial sarcomas (0 of 9), rhabdomyosarcomas (0 of 8), and fibrosarcomas (0 of 7) were BMP-negative. All normal human tissues tested, including the tissues of a 16-week-old fetus, lacked BMP immunoreactivity. Conclusions. Bone morphogenetic protein is expressed in a subset of osteosarcomas, a high proportion of MFHs of bone and soft tissue, and in spindle cell chondrosarcomas. In these tumors, BMP is localized predominantly to the cytoplasm of malignant cells with primitive mesenchymal features; no or little BMP is detected in the more differentiated elements of bone and soft tissue sarcomas. Different histologic types of bone and soft tissue sarcomas may mimic discrete stages of mesenchymal differentiation as defined by BMP expression and histologic criteria. Cancer 1994; 74:842-7. Key words: bone morphogenetic protein, monoclonal antibody, immunohistochemistry, osteosarcoma, malignant fibrous histiocytoma, spindle cell chondrosarcoma.

Background. Bone morphogenetic proteins (BMP) induce ectopic bone formation in vivo and may play a role in normal bone development. In addition, bone morphogenetic activity, as measured in a bone-forming assay in immunodeficient, athymic nu/nu mice, is present in a proportion of osteosarcomas; this activity, which may be mediated by BMP, is correlated with a poor prognosis. Methods. The development of a monoclonal antibody against recombinant human BMP-2, AbH3b2/17, has allowed immunohistochemical localization of BMP in tumor tissues. Cryostat sections of osteosarcomas (21 tumor samples), chondrosarcomas (5 samples), and Ewing's sarcomas of bone (5 samples) were examined with AbH3b2/17 using the avidin-biotin-immunoperoxidase method. Results. The authors found AbH3b2/17 immunoreactivity in 12 of the 21 osteosarcoma samples (57% sensitivity) obtained from 20 patients. For one patient, samples of the primary lesion and a subsequent metastasis were tested, and only the latter showed AbH3b2/17 immunoreactivity. The chondrosarcomas and Ewing's sarcomas examined showed no immunoreactivity. In antigen-positive osteosarcomas, AbH3b2/17 immunostaining was localized predominantly in the cytoplasm of tumor cells. Moreover, the proportion of AbH3b2/17-reactive cells varied among osteosarcomas with disparate histologic features.

An 11-year experience with 100 patients who had surgery as definitive treatment for squamous cell carcinoma of the base of the tongue between 1979 and 1989 has been retrospectively reviewed. Although 81% of the patients had stage Ill or stage IV disease, mandible continuity was maintained in 86%, and the larynx was preserved in 80%. Lymphadenectomy was performed in conjunction with the primary resection in a total of 89 patients, including 62 patients who had clinically evident metastases. Postoperative radiation was administered to 63 patients because of positive resection margins (17), positive cervical lymph nodes (34), or high tumor stage (12). Overall and disease-specific 5-year survival rates for the entire group were 55% and 65%, respectively. The 5-year disease-specific survival rates for stages I/II, III, and IV were 77%, 64%, and 59%, respectively. Local control was achieved in all but 18 patients. Our results indicate that surgery remains a viable treatment option for patients with advanced base-of-tongue cancer. Prospective trials are necessary to compare surgery versus definitive radiotherapy with respect to patients' survival and quality of life.

Our experience with 184 previously untreated patients who had adenoid cystie eareinoma of salivary gland origin is reviewed. Retrospective staging was possible in all but nine patients who had minor salivary gland primary tumors. Sixty-three pereent of patients were diagnosed as having stage I or stage II disease (stage I, 64 patients; stage H, 47 patients), whereas 43 and 21 patients had stage III and IV tumors, respectively. Grading was as follows: eribriform pattern only (grade 1, 126 patients; 68% )9 mixed cribriform and solid features (grade 2, 48 patients; 26%), and solid only (grade 3, 10 patients; 5 % ). Treatment was predominantly surgical ( 174 patients ), and relatively few patients received adjunetive, postoperative irradiation ( 27 patients ). Cumulative 10-year survival was 75%, 43%, and 15% for stage 1, stage II, and stage III and IV patients, respectively, and cause-specific survival at 10 years was as high as 94 % in patients with stage I. disease. Only the clinical stage had a significant impact on survival. Neither survival, regional metastases ( 16 patients; 11% ), nor distant dissemination (64 patients; 43%) was predictable on the basis of tumor grade alone. The prognosis in patients with early stage lesions may be better than has been appreciated.

The expression of tumor-associated glycoprotein (TAG-72), an oncofetal mucin-like tumor-associated glycoprotein derived from membrane-enriched fractions of metastatyic breast carcinoma, has been detected by monoclonal antibody (MoAb) B72.3 in adenocarcinomas of breast, colon, lung, endometrium, pancreas, and ovary. The authors reported the scope of TAG-72 expression detected by MoAb B72.3 in salivary neoplasia. They examined 96 salivary lesions (53 malignant and 37 benign primary tumors, 2 metastatic carcinomas, and 4 other benign lesions) and 17 normal tissues from parotid glands and found: diffuse TAG-72 expression in 29 of 55 (53%) malignant tumors and 6 of 36 (17%) benign tumors and in no normal tissue; focal TAG-72 expression in 10 of 55 (17%) malignant salivary tumors, 10 of 37 (25%) benign salivary tumors (all benign mixed tumors), and 1 of 17 (6%) histologically normal parotid gland ducts. Any expression of TAG-72, whether diffuse or focal, was found to have a 71% sensitivity for detecting salivary malignant tumors, but an unacceptably low specificity for malignant lesions (57%). Alternatively, if only diffuse TAG-72 expression was regarded as indicative of malignancy, the specificity of diffuse TAG-72 expression was 86%, but sensitivity of detection decreased to 53%. The authors studied a subset of benign and malignant mixed tumors (BMT and MMT) and found that 12 of 15 (80%) MMT diffusely and strongly expressed TAG-72, 2 of 15 MMT (13%) expressed TAG-72 focally, and 1 MMT (7%) was nonreactive. By contrast, most BMT did not express TAG-72; only sparse, focal TAG-72 expression was seen in 10 of 27 (37%) BMT. If diffuse TAG-72 expression is considered indicative of malignancy, its sensitivity and specificity for malignant mixed tumors is 80% and 100%, respectively. The authors suggest that diffuse TAG-72 expression may resolve conflicts in determining whether or not a mixed tumor is malignant. Cancer 1992;69:2623-2630.

Carcinosarcomas of the salivary glands are rare lesions that generally have been associated with benign mixed tumors. The authors report a case of a submandibular gland lesion, which occurred in a 64-year-old man, that was composed of intermingled ductal type adenocarcinoma and osteogenic sarcoma with a large component of osteoclast-like giant cells. The local recurrence of the tumor was entirely sarcomatous with no epithelial component observed. There was no histologic evidence of a preexisting or coexisting pleomorphic adenoma. Immunohistochemical studies confirmed two separate populations of tumor cells, corresponding to the histologic growth pattern. The authors review the literature and discuss histogenetic implications of distinction between de novo carcinosarcoma and carcinosarcoma in association with pleomorphic adenoma. Cancer 1991; 69:2031-2035.