Versican expression in pharyngeal squamous cell carcinoma: an immunohistochemical study.

AIMS: To study the expression of versican, a large proteoglycan involved in repressing adhesion between cells and the extracellular matrix in pharyngeal squamous cell carcinoma (PSCC), and its relation to the expression of p53 and catenins, histological differentiation, clinical data, and prognosis. METHODS: For the retrospective survey, primary tumours for analyses were obtained from 118 patients diagnosed with PSCC of the oropharynx or hypopharynx. The immunohistochemical expression of versican was studied and was related to the expression pattern of p53 and catenins, in addition to clinical data and survival. RESULTS: In the primary tumours, strong stromal versican expression was graded as low in 59 (50%) and high in 59 (50%) cases. In addition, intracellular versican staining was seen in nine (8%) tumours. In local lymph node metastases, strong stromal versican staining was significantly more frequent compared with the primary tumours (p = 0.018). Strong stromal versican staining was more frequently seen in less advanced tumours (p = 0.015). There was no association between versican expression and the other investigated variables (p53, catenins, TNM status, and histological grade). Neither stromal nor intracellular versican expression predicted overall survival in these patients. CONCLUSIONS: Versican was more strongly expressed in the stroma of local metastases and in the earlier stages of disease in PSCC. However, versican expression was not an independent prognostic factor in this entity.

Nuclear beta catenin expression is related to unfavourable outcome in oropharyngeal and hypopharyngeal squamous cell carcinoma.

AIMS: To investigate the expression of alpha, beta, and gamma catenins in oropharyngeal and hypopharyngeal squamous cell carcinoma and their relations to each other, as well as to clinical data, tumour differentiation, and prognosis. METHODS: Primary tumours for analysis were obtained from 138 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemistry was used to evaluate the expression of alpha, beta, and gamma catenins. The expression patterns of all catenins were related to clinical data and survival. RESULTS: The expression patterns of all three catenins were significantly interrelated. Reduced gamma catenin expression was significantly associated with poor histological differentiation. No association was found between alpha or beta catenin expression and clinicopathological characteristics. In univariate analysis, patients whose tumours had nuclear beta catenin expression had shorter overall survival than patients with no nuclear expression. In Cox multivariate analysis, nuclear beta catenin expression, tumour status (T class), and Karnofsky performance index were independent prognostic factors of overall survival. CONCLUSIONS: Reduced expression of gamma catenin is associated with dedifferentiation in primary squamous cell carcinoma of the oropharynx and hypopharynx. The fact that nuclear beta catenin expression independently predicts short overall survival suggests that it might be a valuable prognostic marker in pharyngeal squamous cell carcinoma.

The incidence and etiology of postlaryngectomy pharyngocutaneous fistulae.

BACKGROUND: The pharyngocutaneous fistula is troublesome complication after total laryngectomy. Despite a large number of studies, there is still disagreement on factors predisposing to this complication. METHODS: A retrospective analysis of pharyngocutaneous fistulas in 133 patients in whom total laryngectomy was performed. RESULTS: Fistulas were found in 15% of the patients. Spontaneous closure was noted in 80%. Simultaneous laryngectomy and partial pharyngectomy or neck dissection increased the risk of fistula formation. Preoperative irradiation, short interval between radiotherapy and operation, and cobalt/roentgen radiation instead of photons predispose to this complication. The fistulas appeared earlier, and the sizes of fistulas were significantly larger in patients with previous irradiation than those in patients with no preoperative irradiation. CONCLUSIONS: Postoperative pharyngocutaneous fistulas significantly increase patients' morbidity and hospital stay. Good surgical technique and postoperative treatment should be paid attention to patients with an increased risk of pharyngocutaneous fistula formation.

Surgical management of irradiation failures in T1-T2 squamous cell carcinoma of the glottic larynx.

BACKGROUND: The purpose of this study was to analyse the results of salvage surgery after failure of irradiation to control the primary T1-T2 glottic cancer. MATERIALS AND METHODS: Ninety-eight patients with T1 and T2 squamous cell cancer of the glottic larynx were treated with curative intent by radiotherapy. The tumour recurred in 22 of the 98 (22%) patients. Surgical management consisted of total and frontolateral laryngectomy. Survival rates were calculated from the date of the salvage operation. RESULTS: Two of the 22 patients refused to undergo salvage surgery and one patient had pulmonary metastasis. Of the 19 patients who underwent salvage surgery, 14 (74%) had total laryngectomy and 5 (26%) had frontolateral laryngectomy. The operations were curative in 15 (79%) of the 19 patients. The overall 5-year survival rate after surgery was 78%. CONCLUSION: Stringent follow-up of patients with irradiated T1 and T2 glottic laryngeal cancer is essential to permit a successful salvage.

Hypothyroidism after radiotherapy for laryngeal cancer.

PURPOSE: To investigate the incidence of hypothyroidism after radiotherapy of laryngeal cancer, including the possible factors that could predict the onset of hypothyroidism. MATERIALS AND METHODS: We report this study on patients treated by radiotherapy as part of the treatment for laryngeal cancer in the Department of Oncology in Eastern Finland. Sixty-five males and seven females were treated with radiotherapy between 1974-1995.Thyroid function was determined by measuring serum thyroid stimulating hormone, and serum free thyroxine (FT4). The studied risk factors for hypothyroidism included age, treatment modalities, radiation dose and energy, height of the radiation field, and follow-up time. RESULTS: Hypothyroidism was detected in 17 (24%) of the 72 patients. Hypothyroidism was clinically unsuspected in all but one patient. Hypothyroidism was more common, if the height of the radiation field was >/=7 cm, or the patient had been operated. Hypothyroidism was less common if less than a half of the thyroid bed was irradiated. CONCLUSION: The detection of hypothyroidism clinically is difficult, and the rate of hypothyroidism warrants routine assessment of thyroid function after irradiation of laryngeal cancer.

Is the subsite distribution of laryngeal cancer related to smoking habits?

In Finland traditionally as many as two-thirds of laryngeal cancers have been considered to be supraglottic, while in other countries the majority are glottic. The Finnish observation is based on clinical series diagnosed and treated mainly before the 1960s. The aim of our study was to evaluate the present situation. This study consisted of 279 patients treated in Eastern Finland between 1975 and 1994 and included 145 (52%) glottic, 124 (44%) supraglottic and 10 (4%) subglottic tumours in 260 (93%) men and 19 (7%) women. During this study period, the proportion of glottic tumours remained stable in men but increased in women. The change in smoking habits seems to be the most important reason for the shift from supraglottic to glottic tumours.

Downregulation of p21/WAF1 is related to advanced and dedifferentiated laryngeal squamous cell carcinoma.

AIM: To analyse p21/WAF1 expression and its relation to p53, apoptosis, cell proliferation, clinicopathological characteristics, and patient survival in human laryngeal squamous cell carcinoma. METHODS: Primary tumours for analyses were obtained from 172 patients with complete follow up data. All patients were treated between 1975 and 1995. Immunohistochemistry was used to evaluate the expression of p21/WAF1, bcl-2, and p53 proteins. The proliferative activity was determined using Ki67 and PCNA antibodies as well as volume corrected mitotic count (M/V index). Volume corrected apoptotic count (A/V index) was determined using an enzymatic in situ cell death detection kit based on the TUNEL method. RESULTS: High p21 expression was significantly related to high p53 and normal bcl-2 expressions as well as low mitotic count. No association was noticed between p21 expression and apoptotic rate. A significant inverse correlation between p21 expression and advanced stage and poor differentiation was observed, but p21 expression showed no correlation with survival. CONCLUSIONS: The expression of p21 was associated with tumour stage, histopathological grade, node status, and mitotic count, which may indicate a role for p21 in the progression of laryngeal squamous cell carcinoma.

Cytoplasmic accumulation of alpha-catenin is associated with aggressive features in laryngeal squamous-cell carcinoma.

Aberrations in the function of alpha-catenin (alpha-cat), the anchoring protein of E-cadherin, are believed to cause dysfunction of the cadherin-catenin complex, leading to disturbed cell-cell adhesion. It has been suggested that expression of alpha-cat in human tumours might be a better indicator of aggressive phenotype than expression of E-cadherin. The value of alpha-cat as a prognostic marker in laryngeal squamous cell carcinoma (LSCC) is unclear. To determine the potential prognostic significance of alpha-cat, paraffin-embedded samples from 159 patients with invasive carcinoma left in the section and with long-term follow-up were evaluated immuno-histochemically for alpha-cat expression, and the results were related to histopathological grade, tumour stage and survival. Two patterns of staining were observed: pure membranous staining (57%) and membranous staining with cytoplasmic involvement (43%). Cytoplasmic involvement of alpha-cat was associated with dedifferentiation, advanced tumour stage and nodal status. In addition, supra-glottic tumours showed more often cytoplasmic involvement of alpha-cat than glottic tumours. Patients with cytoplasmic involvement appeared to have a trend towards poor overall survival, though without statistical significance. These results suggest that cytoplasmic involvement of alpha-cat is associated with aggressive behaviour and metastatic phenotype of LSCC.

Cancer risk after adjuvant chemo- or chemohormonal therapy of breast cancer.

This study is based on 194 patients with primary breast cancer treated with adjuvant CNF combination chemotherapy, who were followed-up for the risk of subsequent neoplasms. During an average follow-up of 4.8 years, 16 cases of new cancers were detected. Nine non-breast cancers were observed versus 2.2 expected (standardized incidence ratio 4.2). Of the patients with subsequent malignancies, 88% had received antiestrogen (chemohormonal adjuvant therapy); the percentage among all patients was 25%. We conclude that the benefit derived from adjuvant therapy of breast cancer may be reduced because of an increased risk of subsequent cancers.

Hepatic toxicity caused by adjuvant CMF/CNF in breast cancer patients and reversal by tamoxifen.

The purpose of the study was to determine the effect of adjuvant chemotherapy on liver enzymes in breast cancer patients. Furthermore, the effect of tamoxifen on liver enzymes was analyzed. Liver function tests from 194 breast cancer patients who received adjuvant chemotherapy with or without tamoxifen (TAM) were reviewed. Statistically very significant increases were seen in alkaline phosphatase, aspartate acetyl transferase, and gamma glutamyl transferase levels in these patients receiving adjuvant chemotherapy. No statistical changes were noticed in bilirubin levels. If tamoxifen was given together with adjuvant chemotherapy, no changes in liver function tests were detected. Hepatic toxicity was induced in breast cancer patients by adjuvant CMF/CNF therapy (cyclophosphamide, methotrexate, 5-fluorouracil, mitoxantrone). These changes were mostly mild. Adjuvant tamoxifen reduced the increase in liver enzymes caused by adjuvant chemotherapy.

CNF combination as adjuvant treatment in breast cancer patients is well tolerated.

In this study 194 women with breast cancer received adjuvant CNF combination therapy (cyclophosphamide, mitoxantrone and 5-fluorouracil). The side effects and acute toxicity of the regimen were recorded. Although myelosuppression is the dose-limiting factor of the CNF regimen, it was well tolerated and side effects were limited. This regimen induced no cardiotoxicity or irreversible alopecia. It is concluded that CNF is suitable as adjuvant chemotherapy for breast cancer patients.