Prognostic Value of S-Phase Fraction and DNA Ploidy in Oral Carcinoma Studied with Bromodeoxyuridine Labeling in vitro and Flow Cytometry

Abstract

Cellular DNA content abnormalities as well as in vitro bromodeoxyuridine (BrdUrd) labeling was assessed simultaneously by flow cytometry in 62 primary squamous cell carcinomas of the oral cavity. DNA aneuploidy proved to be a striking indicator of malignancy progression. The proportion of aneuploid tumors increased with stage (Tl: 17%; T2: 74%; T3: 90%) as well as with histologic grade (Gl: 25%; G2: 70%; G3: 91%). Only one of 24 patients with metastatic disease had a diploid primary tumor. BrdUrd/DNA flow cytometry of aneuploid tumors allowed selective assessment of proliferation of tumor cell populations alone by excluding non-malignant diploid cells. Prognostic implications of the aneuploid BrdUrd labeling indices (5.2% ± 3.8) could not be confirmed in spite of the remarkable individual differences (.6%–18.1%). Cellular proliferation in oral cancer appears to represent a parameter of individual tumor growth rather than a marker of malignancy progression.

S‐phase fraction and DNA ploidy in oral leukoplakia

“…The proportion of aneuploid tumours increased with stage as well as histologic grade. Only one of 24 patients with metastatic disease had a diploid primary tumour 9 . Oya and Ikemura found that an SPF greater than 27% was the most important parameter for predicting regional metastasis in oral cancer 10 .…”

Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

“…Along this line, an early report indicated that DNA aneuploidy proved to be a prognostic indicator of malignancy progression in oral cancer [14]. Recently, it has also been proposed that DNA ploidy analysis helps to identify oral epithelial dysplasia with a high risk of malignant progression [15].…”

“…Whatever hypothesis is true, it is expected that large genomic changes such as DNA aneuploidy, should be found more frequently associated with OPMLs arising from subsites at high risk of cancerization than in low risk subsites. Along this line, an early report indicated that DNA aneuploidy proved to be a prognostic indicator of malignancy progression in oral cancer [ 14 ]. Recently, it has also been proposed that DNA ploidy analysis helps to identify oral epithelial dysplasia with a high risk of malignant progression [ 15 ].…”

Anticancer Drug Action Assessed by Serial DNA Flow Cytometry during Induction Chemotherapy in Oral Squamous Cell Carcinoma: Impacts on the Development of Individualized Treatment Strategies

“…That tumor progression can be interrupted in diploid oral carcinomas even by surgery alone, but failed to be curative in the majority of aneuploid cases treated similarly, has re cently been reported [4], Lymph node in volvement nearly exclusively in patients with aneuploid primary tumors [6][7][8] represents a further indication that aneuploid oral carci noma cells, unlike diploid tumor cells, indeed share the property of an increased biological malignancy in terms of an enhanced potential of invasion and metastasis, probably acti vated by the cytogenetic events associated with aneuploidy formation.…”

“…The 5-year overall survival rate in patients with diploid carcinomas was 88%, in contrast to only 36% in the aneuploid group. Furthermore, cervical lymph node involve ment has only occasionally been seen in oral carcinoma patients with primary tumors con sisting exclusively of diploid cells, while more than 90% of all patients with lymph node metastases at presentation belonged to the aneuploid group [6][7][8],…”