An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers.

Prognostic information is essential for the evaluation, judgement and optimal treatment of patients with squamous cell cancers (SCCs) of the upper aerodigestive tract. Using immunohistochemical and flow cytometric techniques, we have studied the significance of cellular expression of the Ki-67 antigen, epidermal growth factor receptor (EGFR), the transferrin receptor (TFR) and DNA ploidy status in a prospective analysis of patients with SCCs of the head and neck region. All 42 fresh tumour samples (five well differentiated; 28 moderately differentiated; nine poorly differentiated) expressed both EGFR and TFR to varying degrees. Receptor expression was most marked on the peripheral invading margin of cancer cell islands although staining was also demonstrated in a random fashion within cellular islands and consistently along the basal cell layer of overlying stratified squamous epithelium. The percentage of cancer cells that reacted with the Ki-67 monoclonal antibody was assessed as low (less than 10%) in 15 samples (35.8%), intermediate (10-30%) in 19 samples (45.2%) and high (greater than 30%) in eight samples (19.0%). Eleven of 15 samples (73%) with a low percentage reactivity were DNA diploid, whereas seven of eight samples (87.5%) with a high percentage reactivity were DNA aneuploid. Poorly differentiated SCCs were significantly more often aneuploid than were either moderately or well differentiated tumours. Our results suggest that EGFR and TFR are widely distributed on SCCs, especially on proliferating cells at the invading tumour margin. In addition, there is a close spatial correlation between cells expressing EGFR, TFR and those expressing the Ki-67 antigen. Tumours in which the staining intensity for both EGFR and TFR was intense invariably expressed the Ki-67 antigen in a high proportion of cells. Further patient follow-up will be important in determining whether intense EGFR and TFR staining, combined with a high percentage reactivity with Ki-67 antibody and DNA aneuploidy, will ultimately define a subset of head and neck cancer patients with a poor clinical outcome.

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

[Demonstration and organizational structure of the DNA of human papillomaviruses in laryngeal and hypopharyngeal carcinomas]. / Nachweis und Organisationsstruktur der DNS menschlicher Papillomviren beim Kehlkopf- und Hypopharynxkarzinom.

Thirty biopsy specimens from various histological types of human carcinomas of the larynx and hypopharynx were analysed for the presence of human papillomavirus (HPV) DNA: DNA from the individual specimens were tested for the presence of homologous sequences to HPV genotypes 1, 2, 4, 8, 9, 10, 11, 13, 16 and 18. One squamous cell carcinoma of the hypopharynx (postcricoideal area) contained multiple copies of DNA hybridizing under stringent conditions with HPV 16 DNA. The latter DNA has been found to be frequently associated with human genital cancer. HPV 16 DNA was found mostly episomally as oligomeric circles of 7.9 kbp size, and as larger rear-ranged circular molecules. Integration of the viral DNA in the host cell DNA seems quite likely. Integration and rearrangement of viral DNA into cellular DNA may play a role in the induction and maintenance of the transformed state. The presence of sequences reacting under semistringent conditions with HPV DNA was observed in two additional biopsy specimens of this study. This could suggest that additional laryngeal cancers are associated with papilloma virus infections.

Estrogen and progesterone receptors in head and neck cancer.

The existence of hormone receptors on or within neoplastic tissue has potential diagnostic, therapeutic, and prognostic importance. It was the purpose of this study to measure estrogen and progesterone receptors in a large group of patients with head and neck cancer to determine their frequency. Sixty-five patients with head and neck tumors underwent a total of 75 estrogen and 50 progesterone receptor assays. In this group, 87.7% were squamous cell carcinoma. In the estrogen receptor assays, 89.3% (67/75) were negative, 8% (6/75) were borderline, and only 2.7% (2/75) were positive. In the progesterone receptor assays, 78% (39/50) were negative, 22% (11/50) were borderline, and there were no positive results. There were no changes in assays of tissue removed at biopsy v tissue removed during surgery. There was no impact with chemotherapy. In conclusion, head and neck cancers do not appear to possess estrogen or progesterone receptors and can be considered to be hormonally independent.

Nasopharyngeal lymphoepithelioma. Histological diagnosis as aided by immunohistochemical demonstration of keratin.

Eight cases of primary and metastatic nasopharyngeal lymphoepithelioma and four cases of malignant lymphoma of the pharyngeal region were studied for the presence of keratin by indirect immunofluorescence microscopy. The results showed that all the cases of primary and metastatic lymphoepithelioma contained keratin-positive cells, whereas all the lymphomas were negative for keratin. Anti-keratin antibody thus seems to be a valuable aid in the differential diagnosis between lymphoepithelioma and lymphoma.

[Carcino-embryonic antigen assay in cancer of the upper respiratory and digestive tracts]. / Le dosage de l'antigène carcino-embryonnaire dans les cancers des voies aéro-digestives supérieures.

Radioimmunological assay of carcino-embryonic antigen (CEA) was performed in 238 patients with cancer of the upper respiratory and digestive tracts after a minimum follow-up period of 3 years. Secretion of CEA was observed in only 1 out of 3 cases, levels, always being low and only slightly influenced by the localization or size of the tumor, and the condition of the lymph nodes. Initial levels are of no prognostic significance. The appearance of high levels during the course of the disease corresponds to shorter survival, but as it does not precede clinical evidence of recurrence or metastases this assay cannot play a role as a tumor marker.

[Clinical observations and therapy of the papillomas of the mucous membrane in the otorhinolaryngology (author's transl)]. / Klinik und Therapie von Schleimhautpapillomen im HNO-Bereich.

It's possible papillomas of oral, pharyngeal and laryngeal regions concerning clinical and prognostical aspects to divide under a unit principle. In addition to the criterion of juvenile/adult you must consider solitary or multiple appearance, as well as the macroscopical keratinization. An adequate classification under the aspect of the different malignancy on the basis of morphological and clinical examination of 30 papillomas is proposed. The group of adult, multiple and unkeratinized papillomas of the larynx shows in opposite of opinions of today a tendency of malignancy. Infusion therapy with Bleomycin leads to a volume reduction and to a prolongation of the interval on the papillomas of the larynx, who tend to a malignant degeneration and to a short interval.