Primary Laryngeal Tumors Research Articles

MHC class I antigens and tumour-infiltrating leucocytes in laryngeal cancer: long-term follow-up.

Alteration in MHC class I expression may be used by cancer cells to avoid immune destruction. Much experimental evidence supports this idea, although survival studies are very scarce. To investigate whether the presence or absence of HLA-A, -B and -C antigens in laryngeal carcinoma influences survival, a series of 60 primary laryngeal tumours treated surgically and normal tissues were evaluated in frozen sections for the expression of MHC class I antigens and tumour-infiltrating leucocytes (CD3, CD4, CD8, CD11b, CD1, CD20 and CD16), using monoclonal antibodies and the APAAP, technique. Long-term follow-up from the patients is available, ranging from 6 to 10 years. Thirteen tumours presented total HLA-ABC loss, five selective losses of HLA-A antigens and one absence of HLA-B antigens. Total losses were statistically associated with several clinical and pathological parameters, but there were no differences regarding tumour-infiltrating leucocytes. After conducting a prospective study, only T and N staging and scoring according to Glanz's malignancy classification were found to be independently related to patients' outcome. From our data, we conclude that neither complete loss of HLA class I antigens nor tumour-infiltrating leucocytes appear to influence survival in squamous cell carcinoma of the larynx.

Ras gene mutations and HPV infection are common in human laryngeal carcinoma.

To evaluate the role of ras activation and human papillomavirus (HPV) infection in laryngeal carcinoma, we analyzed tumor DNA from 43 cases, including 25 primary laryngeal tumors, 12 lymph-node and one skin metastases, and 5 recurrent laryngeal carcinomas. Thirteen normal laryngeal tissues and 7 benign laryngeal nodule biopsy specimens along with normal tissue surrounding laryngeal carcinoma in 2 cases were also included. The polymerase-chain-reaction technique was used to amplify DNA fragments containing codon 12 and 61 of H-, K- and N-ras, also HPV 16, 18 and 33 DNA, subsequently hybridized with sequence-specific oligonucleotides. DNA samples from 22 patients with laryngeal carcinoma revealed ras mutations (18 in N-ras codon 12, 6 in H-ras codon 61, and 3 in K-ras codon 61). Likewise, HPV DNA was found in 16 cases (HPV 16, 18 and 33 in 3 cases, 14 cases and 1 case respectively). ras mutations were significantly higher in metastatic tumors (10 of 13 cases) than in primary (11 of 25 cases) and recurrent laryngeal carcinomas (1 of 5 cases). HPV DNA was detected in 60% of recurrent, 44% of primary and 15% of metastatic tumors. Only 2 of the 13 normal laryngeal tissues and 1 out of 7 laryngeal nodule specimens were found to contain HPV DNA. These results suggest that ras activation, especially in N-ras codon 12.1 (GGT-->AGT) and HPV infection are 2 important factors in (multistage) laryngeal carcinogenesis. The ras mutation may be associated with metastatic ability of the tumor.

EGF receptor expression in primary laryngeal cancer: Correlation with clinico‐pathological features and prognostic significance

Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease-free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub-set of laryngeal-cancer patients with a particularly unfavorable prognosis.

Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors

The authors investigated the presence of epidermal growth factor (EGF-R), estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were expressed in all tumor specimens analyzed, with significantly higher levels in tumor samples compared with normal mucosa (P less than 0.05). The immunohistochemical study demonstrated the presence of EGF-R in basal and parabasal cells of normal mucosa and in most of the cancer cells. There was no correlation between EGF-R and tumor localization or T classification. On the other hand, the authors did find an interesting correlation between EGF-R levels and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors. Moreover, the three patients whose tumors expressed the highest EGF-R levels had disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5% expressed very low but detectable ER, PR, and AR levels, respectively. No statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens, and neither was there any correlation of ER, PR, and AR with the pathologic findings. The authors' results suggest that the EGF-R system may play a role in regulating the growth of laryngeal cancer. Additional studies should demonstrate whether, as in other tumor types, EGF-R expression may have prognostic significance in human laryngeal cancer.

Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx

A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies and the APAAP technique. We found 13 tumours presenting total HLA-ABC loss, five with selective loss of HLA-A antigens and one with absence of HLA-B antigens. These losses were statistically associated with clinical and pathological parameters, such as T stage, degree of differentiation, scores according to the Jakobsson and Glanz grading systems and degree of leukocytic infiltration. Our results lead us to the following conclusions: (a) HLA class I losses were found in a group of tumours showing greater aggressiveness and worse prognosis; (b) these alterations in expression were not associated with an increased metastatic potential. Thus, the absence of HLA molecules in laryngeal tumours is related to greater local aggressiveness, and the loss of class I antigens seems to constitute an adaptive tumour mechanism to avoid the different anatomical and immunological barriers within the larynx.

Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx

A series of 38 primary laryngeal and hypopharyngeal tumours, 15 lymph-node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I and II antigens, using monomorphic monoclonal antibodies (MAbs) to HLA-ABC, beta 2-microglobulin, DR, DP, DQ, HLA-B and polymorphic HLA-ABC antigens. Normal distant mucosa of larynx reacted to anti-class I antibodies but not to anti-class II. In 9 primary tumours (23.7%) HLA class I antigens were not observed. The remaining 29 showed a strong reaction to not observed. The remaining 29 showed a strong reaction to anti-HLA-ABC (heavy chain) and anti-beta 2-microglobulin, although in 3 cases out of 29 no staining was observed with anti-HLA-B locus-specific MAbs. These selective losses were confirmed using the corresponding anti-HLA polymorphic MAbs. For HLA class II molecules, only DR was observed in 3 of 38 cases. Defective HLA class I expression statistically correlates with high scores according to Jakobsson's criteria for histopathological tumour grading. Loss of HLA-ABC antigens was most frequent among the cases with poor differentiation (6/8 cases). On the contrary, class II antigen expression was correlated with a well differentiated pattern and a more favourable prognosis (p less than 0.001). We have found differences in HLA class I expression when comparing primary tumours and autologous metastases (3/9 cases). Immunoprecipitation and SDS-PAGE of class I antigens, Northern and Southern blot analyses of MHC class I genes were performed. We have not detected class I gene rearrangement using HLA coding and locus-specific non-coding probes. However, we have found a class I transcription defect that corresponds with a class-I-negative phenotype.

Association of laryngeal and pulmonary malignancies: a continuing challenge.

Over a 10-year period, 790 patients with squamous cell carcinoma of the head and neck were treated at The Medical College of Wisconsin Affiliated Hospitals and were followed for a minimum of 7 years. Of the 218 patients with index primary laryngeal tumors, 43 (19.7%) developed additional malignancies in the head and neck, esophagus, or lung. Secondary lung tumors were the most common, occurring in 23 patients (10.6%). Of the 218 patients with index primary laryngeal carcinoma, 113 were treated successfully and never developed a recurrence of the original tumor. Twenty-one second primary lung malignancies developed in this group of successfully treated laryngeal tumor patients. The occurrence of these pulmonary malignancies was distributed fairly evenly over time. Three patients developed second primary lung tumors more than 7 years after initial treatment. The appearance of a secondary malignancy in the lung had a devastating effect upon survival. None of our patients survived more than 2 years after detection of the lung lesion. The relatively high incidence and delayed onset of second primary lung tumors in this group call into question the concept of 5-year "cures." Our challenge for the future should be the prevention and early detection of these second primary lung tumors.