Clinical Significance of Cytophotometric Analysis on Nuclear DNA Content in Squamous Cell Carcinoma of the Tongue

In order to elucidate the clinical significance of nuclear DNA analysis in the primary squamous cell carcinoma (SCC) of the tongue, cytophotometric studies were performed. Initial biopsy materials were obtained from 53 patients with tongue carcinoma, who were treated at the Department of Oral Surgery of Sapporo Medical College Hospital during the period of 1976-84. The paraffin section for cytophotometric DNA analysis with Feulgen stain was made from the portion just adjacent to the section stained with hematoxylin-eosin. The nuclear DNA contents of the cancer cells at the tumor-host boundary were measured by cytophotometry using a cytophotometer (Nikon, SPM-RFL System). The following results were obtained. (1) The mean and standard deviation of nuclear DNA contents of carcinoma in the 53 patients varied from case to case. Almost all of the DNA histograms were of various widths differing from those of the normal population. (2) On the basis of the degree of dispersion and modal DNA value of each DNA histogram, all DNA histograms were graded in four patterns such as P-I (diploid pattern), P-II (hyperdiploid pattern), P-III (narrow aneuploid pattern) and P-IV (wide aneuploid pattern). (3) The relationship between the grades of DNA patterns and the clinical findings were analysed. Carcinomas of T1, 2, stage I, II and exophytic type were mostly P-I, II of DNA histograms, but on the other hand, those of T3, 4, stage III, IV and endophytic type tended to be P-III, IV of DNA histograms. (4) Each DNA pattern was related to cellular differntiation, nuclear size and mode of cancer invasion (M-1, 2, 3, 4C, 4D). The frequency of P-I, II was 66.7% in well differentiated SCC, 61.5% in moderately differentiated SCC and 8.3% in poorly differentiated SCC, and those of P-III, IV was 33.3% in well differentiated SCC, 38.5% in moderately differentiated SCC and 91.7% in poorly differentiated SCC. Total number of DNA histograms showed a hyperdiploid pattern in well differentiated SCC, a narrow aneuploid pattern in moderately differentiated SCC and a wide aneuploid pattern in poorly differentiated SCC. Mean and standard deviation of nuclear size was higher in cases of widely distributed DNA histograms than in cases of narrowly distributed DNA histograms. It was shown that the correlation coefficient between nuclear DNA content and nuclear size was 0.68, 0.77 for the mean value and standard deviation, respectively. In regard to the mode of cancer invasion, frequency of P-I, II were 68.6%, in M-1?3 and 16.7% in M-4C, 4D and that of P-III, IV were 31.4% in M-1?3 and 83.3% in M-4C, 4D. Total number of DNA histograms of carcinomas with M-1?3 ?showed a relatively narrow distributed pattern, while that of carcinomas with M-4C, 4D showed a widely distributed pattern. These results showed that the cellular differentiation, nuclear size and mode of cancer invasion were all closely correlated with the DNA pattern. (5) The relationship between DNA pattern and BLM effect was estimated and the prognosis was evaluated from the DNA pattern. The mean value of tumor regression rate with BLM were 73.0%, 44.0%, 21.9% for P-I, P-II, III, P-IV, respectively. A five year cumulative survival rate was 100%, 91.3%, 78.9%, 28.6% for P-I, P-II, P-III, P-IV, respectively. These results showed that the DNA pattern was closely correlated with BLM effect and the prognosis of tongue carcinoma. (6) Malignancy points evaluated from T-category, degree of differentiation, mode of cancer invasion and DNA pattern was classified into four grades, such as grade I (points 4-6), grade II (points 7-9), grade III (points 10-12) and grade IV (points 13-16). Tumor regression rate with BLM were closely correlated to malignancy points (r=-0.62) and the grade in each case. In regards to the prognosis, the five year cumulative survival rates were 100% in grade I, II, 69.0% in grade III and 30.0% in grade IV