Squamous cell carcinoma radioimmunoassay in squamous cell carcinoma of the head and neck

Tumor-associated antigen has shown promise as a clinical aid in the detection and monitoring of uterine cervical squamous cell carcinoma. Antigen levels have been shown to reflect the extent of disease and response to treatment. These findings have suggested that measurements of tumor-associated antigen may be useful in monitoring other squamous cell carcinomas. To test this hypothesis, we measured tumor-associated antigen using the squamous cell carcinoma radioimmunoassay in 103 patients with previously treated squamous cell head and neck tumors and 28 patients with known squamous cell carcinoma of the head and neck. Increased squamous cell carcinoma antigen levels were found in 39 percent of patients with known tumors and in 19 percent of the patients with previous curative resection. The sensitivity of the assay limited its usefulness in predicting the presence of new and recurrent tumors.     

HPV-related squamous cell carcinoma variants in the head and neck

The great majority of HPV-related carcinoma of the oropharynx is nonkeratinizing squamous cell carcinoma. More recently, an increasing number of squamous cell carcinoma variants that are HPV positive are being reported in the oropharynx, as well as in other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, questions raised include whether the virus is biologically active and involved in the pathogenesis of these tumors, and whether there are clinical implications with regard to patient outcome and treatment modality changes that may be needed in HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here include: basaloid squamous cell carcinoma, undifferentiated carcinoma, adenosquamous carcinoma, papillary squamous carcinoma, and small cell carcinoma. Some investigations have suggested a favorable prognosis in some variants, analogous to that of the conventional nonkeratinizing (basaloid) carcinoma, while others showed poorer outcome. So far, the number of studies on this subject is limited and the number of cases evaluated in each investigation is few. Because of this, it is prudent at this stage not to alter management protocols as a result of identification of HPV in these variants and to await additional studies.     

Selective neck dissection in node-positive squamous cell carcinoma of the head and neck

Objective The optimal type of neck dissection in head and neck squamous cell carcinoma (SCC) with clinical cervical metastases has not been determined. The following study was performed to determine the rate of regional control with selective neck dissection (SND) in these patients. Study Design Case series with planned data collection. Settings Single institution, cancer center. Methods and Subjects Patients with cervical lymph node metastases from mucosal cancers of the head and neck who were treated with SND from 2000 to 2010 were selected. Demographics, tumor characteristics, extent of neck dissection, adjuvant treatments, locoregional control, and survival were recorded. Recurrence in the neck and disease-specific survival (DSS) were primary and secondary end points. Results One hundred eight patients underwent SND. Sixty-nine (64%) were male. Median age was 62 (20-89) years. The most common primary site was the oral cavity (71.3%). Ninety-five (88%) received adjuvant treatment. Median follow-up was 21 months. Six patients (5.5%) had isolated recurrence in the dissected neck. Patients with N2C disease had poorer neck recurrence-free survival. At the end of study, 64 (59.3%) patients had no evidence of disease, and 23 (21.3%) had died of disease. Two-year DSS was 76.9%. Number of positive nodes (P = .026) and positive surgical margins (P = .001), among others, were predictors of poorer DSS. Conclusion In a highly selected group of patients with cervical lymph node metastases from head and neck SCC, selective neck dissection is effective in controlling the disease in the neck when performed in the setting of a multimodality treatment, including adjuvant radiotherapy or radiochemotherapy.     

Urokinase receptor up-regulation in head and neck squamous cell carcinoma

BACKGROUND: Urokinase-type plasminogen activator is important for matrix degradation and motility of cancer cells. For effective invasion, urokinase has to be associated with its cell surface receptor.(1) METHODS: We analyzed 33 head and neck squamous cell carcinomas (hnSCC) and 14 mucosal tissue samples for the expression of urokinase receptor using Northern hybridization and correlated expression levels to clinical and histopathologic data. Urokinase expression was determined by fibrin zymography. RESULTS: The expression of urokinase receptor is significantly increased in hnSCC compared with adjacent mucosa. Expression levels in primary tumors show no statistically significant correlations to T staging, metastasis, recurrence, or differentiation stage of the resected tumors. Furthermore, there was no correlation between urokinase and urokinase receptor expression levels in SCC samples. CONCLUSIONS: Urokinase receptor expression is increased in hnSCC, but it is not useful as a prognostic marker for the metastatic behavior of primary tumors. Comparison of our data with previously published reports is discussed.     

Correlation of biomarkers in head and neck squamous cell carcinoma

Objective

To evaluate the relationship of functional magnetic resonance imaging (MRI) parameters, including choline/creatine ratio (Cho/Cr) and apparent diffusion coefficient (ADC) with protein expression of 10 common tumor and prognostic markers in head and neck squamous cell carcinoma.

Study Design

Cross-sectional study.

Setting

University hospital.

Subjects and Methods

The Cho/Cr and ADC obtained from 74 patients with head and neck squamous cell carcinoma were correlated with the expression level of the 10 protein markers as determined by immunohistochemistry.

Results

Cho/Cr showed significant positive correlations with cyclooxygenase 2 in primary tumors (r = 0.714), and epidermal growth factor receptor in metastatic cervical lymph nodes (r = 0.522). ADC showed significant (r = −0.591) negative correlation with human epidermal growth factor receptor 2 in metastatic cervical lymph nodes.

Conclusion

There are relationships between protein and functional MRI markers. Future research in this direction may improve our understanding of the cancer micro-environment.     

Efficacy of neck treatment in patients with head and neck squamous cell carcinoma

BACKGROUND: Treatment of head and neck squamous cell carcinoma (HNSCC) addresses the primary tumor and the lymphatic drainage. Modalities for the neck are neck dissection and/or radiation therapy. In most cases, the neck is treated by the modality that seems more appropriate for the primary. The aim of this study was to analyze the results of the neck treatments either by neck dissection alone, by radiation therapy alone or by neck dissection followed by radiation therapy. METHODS: This was a retrospective chart analysis of 699 patients treated for a previously untreated HNSCC. The primary endpoint was recurrence at the treated neck. RESULTS: Two hundred eighty-one (40%) patients underwent primary neck irradiation, 219 (31%) neck dissection alone, and 199 (29%) neck dissection followed by adjuvant irradiation. The 5-year regional control rates after neck dissection alone were 83% for pN0, 75% for pN1, 60% for pN2a, 59% for pN2b, and 50% for pN2c; after radiation alone, 89% for cN0, 87% for cN1, 40% for cN2a, 60% for cN2b, and 48% for cN2c; and after neck dissection with adjuvant radiation, 86% for pN0, 96% for pN1, 100% for pN2a, 88% for pN2b, and 88% for pN2c. CONCLUSIONS: Radiation or neck dissection alone are efficient to control early neck disease. For advanced N2/3 neck disease, neck dissection followed by adjuvant radiation is highly efficient, whereas primary radiation results in a high number of regional failures. The literature suggests planned neck dissection to improve regional control for these patients.     

Radiotherapy for basaloid squamous cell carcinoma of the head and neck

Basaloid squamous cell carcinoma (BSCC) of the head and neck is a recently described high-grade variant of squamous cell carcinoma. It is a biologically virulent neoplasm with a propensity for nodal, as well as systemic, metastases. Because of the limited number of published reports, we reviewed data from patients of the University of Virginia Health Sciences Center and identified 16 cases of BSCC. The intent of this study was to determine the role of radiotherapy in the treatment of BSCC and better define the clinical features of this entity. Radiotherapy alone, or in combination with surgery, resulted in excellent local control rates. Distant metastases, chiefly pulmonary, occurred in more than half of the patients.     

Skin metastases in squamous cell carcinoma of the head and neck.

Distant metastases in squamous cell carcinoma of the head and neck (SCCHN) are most often to the lung, liver, and bone. SCCHN rarely metastasizes to skin sites. OBJECTIVE: To ascertain the significance of skin metastases (SM) on the prognosis of patients with SCCHN. METHODS: A retrospective review of all patients between 1987 and 1999 with SCCHN was conducted. Patients in whom SM developed were identified. Data pertaining to demographics, primary tumor staging, SM development, and outcome were investigated. RESULTS: In 798 consecutive patients diagnosed with SCCHN between 1987 and 2000, 19 developed SM. The average time of onset of the SM was 17.65 months. The average survival time was 7.2 months after the development of SM. The overall survival time of patients who developed SM from the initial presentation of the primary tumor was 24.85 months. The 1-year survival rate from the time of development of SM was 0%. CONCLUSIONS: Metastasis to skin sites is an uncommon feature of SCCHN. SM may represent the first clinical evidence of impending loco-regional recurrence or distant metastasis. The development of SM is an ominous sign associated with an extremely poor prognosis, similar to the development of distant metastasis at more typical sites. Both the development of SM and survival of patients developing SM are independent of primary tumor stage. Current treatment options of SM are limited in their efficacy.     

Perineural invasion in squamous cell skin carcinoma of the head and neck

On review of 520 patients with 967 squamous cell carcinomas of the skin of the face treated at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston during a 10 year period, 14 percent of the patients were noted to have perineural extension of tumor. Study of the patients with perineural tumor demonstrated an increased incidence of spindle cell and adenosquamous cell types, an increased incidence of cervical lymphadenopathy and distant metastasis, and significantly reduced survival curves compared with those of patients with squamous cell skin carcinoma without perineural invasion. Tabulation confirmed that the maxillary and mandibular branches of the trigeminal nerve and the facial nerve were most commonly involved. For patients with squamous cell skin carcinomas with perineural invasion, aggressive therapy is recommended, specifically, resection of involved tissues and nerves and appropriate regional lymphadenectomy followed by postoperative radiotherapy. This plan affords the best opportunity for tumor control. The indications for exploration of the middle fossa of the intracranial portion of the trigeminal nerve deserve further study.     

Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma

BACKGROUND: Serine proteases have important roles in tumor invasion and metastasis, and their inhibitors, serine protease inhibitors (serpins), are attractive targets for therapeutic strategies. On chromosome 18q21, there is a cluster of serpins: maspin, headpin, and squamous cell carcinoma antigen 1 (SCCA1)/SCCA2. Others and we have reported that the expression of these serpins is down regulated in head and neck squamous cell carcinoma (HNSCC) cells compared with normal squamous epithelial cells. In this study, we hypothesized that expression of SCCA1 is biologically disadvantageous to HNSCC cells. METHODS: HNSCC cell lines were transfected with a mammalian expression vector with SCCA1 cDNA. In vitro proliferation, migration, or invasive potential (matrigel assay) of the transfectants were assayed. In addition, the in vivo growth and invasion was analyzed using the floor-of-mouth model of nude mice. RESULTS: SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 expression significantly inhibited the in vitro invasion in matrigel assays. Furthermore, the in vivo growth and invasion in nude mice was also inhibited by SCCA1 expression. CONCLUSIONS: Overexpression of SCCA1 in a HNSCC cell line inhibited its invasive potential. Loss of expression of the serpin SCCA1 may play a role in the malignant progression of HNSCC.     

Molecular mediators of metastasis in head and neck squamous cell carcinoma

BACKGROUND: The presence of regional metastasis in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis and high mortality. Although significant improvements in standard therapies have increased the efficacy of local tumor management, the high incidence of tumor recurrence has resulted in limited improvements in overall survival rates. Understanding the molecular mechanisms that mediate HNSCC invasion and metastasis may enable identification of novel therapeutic targets for the prevention and management of tumor dissemination. METHODS: A literature review was performed. RESULTS: Several biologic mediators and mechanisms that have been implicated in HNSCC metastasis, such as cell adhesion molecules, proteolytic enzymes, growth factor signaling, metastasis suppressor genes, and chemokine receptors were reviewed. CONCLUSIONS: Prevention of HNSCC metastasis is an important clinical objective that requires an increased understanding of the molecular mechanisms of tumor invasion and dissemination.     

In vitro stem cell assay in head and neck squamous carcinoma

Squamous cell carcinoma of the head and neck was successfully cultured from 33 of 73 specimens (45 percent) using the soft agar technique developed by Hamburger and Salmon. Successful cultures were evenly divided between biopsies of primary tumors and metastases; no growth and contaminated specimens predominantly came from biopsies of primary tumors. Prediction of viability before plating with trypan blue was unreliable. The cloning efficiencies in each histologic grade had a wide range, but the median cloning efficiency was higher for poorly differentiated tumors. Six of 11 patients with cloning efficiencies greater than 0.02 percent were dead of disease within 3 months, whereas only 1 of 16 patients with cloning efficiencies less than 0.02 percent was dead of disease at 3 months (p < 0.01). In vitro chemotherapeutic drug sensitivity testing correctly predicted in vivo resistance in three patients. The in vitro stem cell assay should prove a useful tool for clinical and biologic studies of head and neck cancer.