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These predictive markers should be included in future clinical trials of advanced laryngeal cancer to determine their usefulness prospectively.

Although genetic alterations of chromosome band 9p21 ± 22 occur frequently in head and neck squamous cell carcinoma (HNSCC) cell lines, alterations of the cyclindependent kinase inhibitor p16 INK4a located in this region are less common in corresponding primary tumors. To further investigate genetic alterations at 9p21 ± 22 and p16 INK4a in primary HNSCC, a paired set of 21 tumors and blood specimens that were shown previously to exhibit allelic loss at 3p and elsewhere, were tested for LOH at 9p21 ± 22 using eight di erent highly polymorphic marker. Sixteen of the samples (81%) exhibited LOH for at least one marker. Frequent LOH was found surrounding p16 INK4a and at three additional noncontiguous regions of 9p21 ± 22. No homozygous deletions were identi®ed. SSCP screening and direct sequence analysis led to the identi®cation of mutations the p16 INK4a gene in two tumors. p16 INK4a was not hypermethylated in any of the samples studied. Furthermore, there was no correlation between LOH at 9p21 ± 22 and the RB1 tumor suppressor gene. These ®ndings indicate that in the set of tumors that we tested, LOH at 9p21 ± 22 is common in primary HNSCC but that genetic alterations of p16 INK4a located in this region are unusual. Additional tumor suppressor genes at 9p21 ± 22 may therefore be involved in the pathogenesis of this tumor.

Background. Alterations in DNA content, nuclear morphologic characteristics, and histologic grading have been associated with prognosis in several types of solid malignant neoplasms. Methods. To determine the potential usefulness of these factors in predicting tumor behavior in patients with laryngeal squamous cell carcinoma, tumor specimens from 88 previously untreated patients with Stage III or IV cancers were studied. The DNA content and nuclear area (NA) were measured for individual nuclei of each tumor with the use of Azure A‐stained frozen sections. An adjusted DNA index (aDI) for each patient was calculated from the slope of the linear regression analysis of nuclear DNA index on NA. Hematoxylin and eosin‐stained sections were examined and graded systematically for histologic growth pattern. All patients were enrolled in a prospective clinical trial and had laryngectomy and postoperative radiation therapy. Results. The disease‐free survival length was longer and the relapse rates were lower in patients with a low aDI (P < 0.005) and with tumors exhibiting low‐grade growth patterns (P < 0.001). Conclusions. These parameters were independent of staging variables and were better predictors of tumor relapse than traditional clinical staging classifications.