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BACKGROUND: Basic fibroblast growth factor (bFGF) is a potent angiogenic factor implicated in tumor growth and metastasis. To determine if bFGF and basic fibroblast growth factor receptor 1 (bFGFR1) and 2 (bFGFR2) are upregulated in head and neck squamous cell carcinoma (HNSCC), we measured the distribution and levels of each in HNSCC specimens and control specimens. METHODS: Head and neck squamous cell carcinoma and control tissue specimens were analyzed qualitatively (40 patients, 10 controls) using immunohistochemistry, and quantitatively (26 patients, 8 controls) using immunoassays and graded immunahistochemistry. Control tissue consisted of palatal tissue obtained during uvulopalatopharyngoplasty (UPPP). RESULTS: Immunohistochemical analysis revealed that bFGF, bFGFR1, and bFGFR2 antigens were strongly associated with cancer and vascular endothelial cells in HNSCC. Control tissue had moderate staining of vascular endothelium and no stromal staining. Quantitative analysis of bFGF in tissue homogenates indicated that bFGF levels in cancer specimens were significantly elevated compared with control tissues (420.3 [+ or -] 360.9 ng/ mg total protein versus 49.2 [+ or -] 48.7, respectively, P [is less than or equal to] 0.05). When analyzed by clinical stage, bFGF levels were significantly higher in stage III patients as compared with stage IV patients (P [is less than or equal to] 0.01). When immunohistochemistry results were correlated with clinical stage, bFGF (P [is less than or equal to] 0.01), bFGFR1 (P [is less than or equal to] 0.001), and bFGFR2 (P [is less than or equal to] 0.0001) staining was significantly more intense in the cancer cells of stage III versus stage IV patients. CONCLUSION: Enhanced expression of bFGF and bFGF receptors by cancer and vascular endothelial cells is present in HNSCC, and may contribute to tumor growth and metastasis in HNSCC by mediating angiogenesis. Strategies aimed at decreasing the expression of bFGF and its receptors may be of therapeutic benefit in HNSCC, particularly at an early stage of disease.

BACKGROUND: Angiogenesis is an essential process required for growth and metastasis in cancer. In breast, gastric, and prostate cancer, vascular endothelial growth factor (VEGF) has been implicated in angiogenesis; however, little is known about VEGF in HNSCC. In this study, we hypothesize that VEGF is present in elevated levels in HNSCC and may therefore play a role in promoting angiogenesis. METHODS: We obtained tumor tissue from 63 HNSCC patients undergoing primary resection. All tissue samples were analyzed by immunohistochemistry (IHC) techniques for the presence and localization of VEGF; however, only 36 had sufficient amounts of tissue for quantitative analysis of VEGF by ELISA. Nine control specimens taken from patients undergoing uvulopalatopharyngoplasty were also analyzed. RESULTS: In all 63 of our patient samples we found VEGF to be present and localized to the cancer cells and endothelial cells. The poorly differentiated cancer cells stained more intensely in comparison with the well-differentiated ones. There was a 20-fold increase in the patient levels when compared with controls levels (P [is greater than or equal to] 0.05). Analysis by enzyme-linked immunosorbent assay revealed elevated mean levels of VEGF (241 [+ or -] 326 pg/mg total protein [TP]) with a range of 2 to 1484 pg/mg TP. The control specimens had mean levels of 13 [+ or -] 11 pg/mg TP and a range of 1 to 78 pg/mg TP. Patients who exhibited higher levels of VEGF tended to have a higher rate of disease recurrence (P [is less than or equal to] 0.048) and shorter disease-free interval (P [is less than or equal to] 0.05). CONCLUSIONS: The expression of VEGF in elevated levels in the HNSCC tumor microenvironment appears to be associated with more aggressive disease. Based on our results, VEGF may be an important angiogenic factor associated with cancer cells and endothelial cells in HNSCC. Further studies are needed to better define the role of VEGF in HNSCC and its role as a potential target for therapeutic intervention.

BACKGROUND: Interleukin 8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. We hypothesize that IL-8 plays an important role in the cellular proliferation and angiogenesis seen in head and neck squamous cell carcinoma (HNSCC) and set out to identify its receptors, IL-BRA and IL-ORB. METHODS: Immunohistochemical analysis was performed on specimens from 38 HNSCC patients with stage I to IV disease and control tissues. RESULTS: All of cancer specimens demonstrated positive staining for IL-BRA. The IL-BRA staining of microvessel endothelial cells was seen in 51%. The IL-ORB pattern was similar to the IL-BRA pattern in that 97% of cancer sections demonstrated positive cancer cell staining, and 74% of the specimens demonstrated positive staining for microvessel endothelial cells. CONCLUSION: Our studies demonstrate that IL-8 receptors are expressed by cancer cells and microvessel endothelial cells in HNSCC, suggesting that IL-8 may act in an autocrine/paracrine fashion to stimulate cellular proliferation and angiogenesis.

BACKGROUND: Transforming growth factor beta (TGF-[Beta]) has antiproliferative effects on normal and neoplastic cells that express specific TGF-[Beta] receptors. We hypothesize that diminished expression of TGF-[Beta] and/or its receptors may contribute to the uncontrolled proliferation of head and neck squamous cell carcinoma (HNSCCA) cancer cells. METHODS: Using immunohistochemical techniques, we characterized the expression of TGF-[Beta] isoforms and TGF-[Beta] receptors, TGF-[Beta](RI) and TGF-[Beta](RII), in HNSCCA. Tumor production of TGF-[Beta] was evaluated in culture supernatants from a cytokine-stimulated HNSCCA tumor line (HTB-43). RESULTS: All control specimens displayed strong cell-associated staining of TGF-[Beta] as well as both receptors. Forty-seven of 47 cancer specimens exhibited positive staining for TGF-[Beta] in the tumor matrix. Forty of the 47 cancer specimens demonstrated no expression of TGF-[Beta](RI), and 43 of the 47 expressed no TGF-[Beta](RII). Only interleukin 1 alpha (IL-1 [Alpha]) and IL-1 [Beta] induced significant TGF-[Beta] expression from the HTB-43 cells. CONCLUSIONS: Decreased expression of TGF-[Beta] receptors may play a significant role in the pathogenesis of HNSCCA by allowing uncontrolled cell proliferation.

Cytokines are known to play an important role in host defense by regulating the function, growth, and differentiation of the eelis of the immune system. We hypothesize that, in the tumor microenviroument, tumor cells and resident tissue eelIs (e.g., fibroblasts ) also produce cytokines that may regulate the local immune response to tumors. Initially, homogenates of eight head and neck squumous cell carcinomas (HNSCC) were assayed for the presence of interlenkin-1 (IL-1 ), interleukin-4 (IL-4), interlenkin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GMCSF ) to establish the presence of these cytokines in the tumors in vivo. We detected IL-1 in all tumor homogenates and IL-4, IL-6, and GM-CSF in some homogenates. To assess the ability of HNSCC to produce these cytokines, supernatants of short-tea primary cultures of HNSCC were assayed for the same cytokines. No IL-1 was detected, although baseline levels of IL-4, IL-6, and GM-CSF were present. However, the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 (p These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells. Our data also suggest that IL-I may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells.

Histoplasmosis of the larynx is an uncommon phenomenon, and it is typically not seen in the Northeastern United States. It can appear as an erosive lesion and mimic a squamous [...]

This study retrospectively analyzed 105 patients with squamous carcinoma of the nasal cavity and paranasal sinuses. The primary tumor was located in the maxillary sinus in 65 patients (62 percent), the nasal cavity in 27 (26 percent), the ethmoid sinus in 11 (10 percent), and the sphenoid sinus in 2 (2 percent). Over half of the patients with antral cancer were treated with surgery and radiotherapy, whereas one-third of the remaining patients received combination therapy. Most procedures were radical, including sacrifice of the orbital contents in half of the surgically treated patients. The 5-year determine cure rate was 45 percent for patients with nasal city tumors, 38 percent for those with maxillary sinus lesions, and 13 percent for those with ethmoid tumors. Local recurrence remains a major problem despite aggressive surgery and increased use of adjunctive radiotherapy., The intricate anatomy of the nose is a problem in the treatment of cancer located in the nasal cavity and paranasal sinuses. In addition, early symptoms are often ignored, therefore many patients are in advanced stages of the disease when first treated. Five-year survival patterns vary according to the location of the primary tumor and the method of treatment. The medical records of 105 patients with malignant tumors who were treated from January 1966 to December 1982 were retrospectively analyzed to determine the correlations among the location of the tumor, method of therapy and five-year cure rate. The patients (70 males and 35 females) ranged in age from 27 to 81 years (median age was 60 years). The tumor was in the maxillary sinus in 65 patients (62 percent), in the nasal cavity in 27 patients (26 percent), in the ethmoid sinus in 11 patients (10 percent), and in the sphenoid sinus in 2 patients (2 percent). Either surgery or radiotherapy was performed on over 50 percent of the patients, and the remaining patients received a combination of surgery and radiation. The five-year cure rate was 37 percent for all the patients, but patients with nasal cavity and maxillary sinus tumors had the highest rates at 45 and 38 percent, respectively. The lowest cure rate (13 percent) was found in ethmoid sinus tumor cases, and one out of two sphenoid cancer patients was alive after five years. Local recurrence of the cancer seemed to be a common problem, but the recent development and improvement of computed tomography scanning will be useful in determining the exact extent of the tumor. In addition, modified procedures using a combination of chemotherapy, radiation and surgery (trimodal therapy) to treat nasal and sinus carcinoma may increase the cure rate and decrease the need for radical surgical treatment alone. (Consumer Summary produced by Reliance Medical Information, Inc.)