Intratumoral Heterogeneity of DNA Ploidy and Regional Differences in Epidermal Growth Factor and Epidermal Growth Factor Receptor of Esophageal Carcinoma.

Abstract

Intratumoral regional differences in DNA ploidy patterns, and expression of epidermal growth factor (EGF) and EGF receptor (EGF-R) were studied to evaluate the biological and clinical significance of intratumoral DNA heterogeneity in 23 cases of esophageal carcinoma. Multiple specimens were subjected to histologic grading of carcinoma, DNA analysis and immunohistochemistry. DNA heterogeneity was found in 34.8% of the cases. Expression of EGF and EGF-R within a single tumor was observed in 69.6% and 73.9% of the lesions examined, respectively. A positive correlation was noted between the expression of EGF and that of the EGF-R. EGF expression showed positive correlation with the DNA index, but not with the proliferative index. There was no relationship between DNA heterogeneity and the degree of histopathological differentiation of carcinoma. Cases with DNA heterogeneity showed better prognosis than those with DNA homogeneity. The present study suggests that esophageal carcinoma consists of carcinoma cells with intratumoral regional polymorphism and variable types of clones. Furthermore, the autocrine mechanism of EGF and EGF-R could be one of the contributory factors on the development of DNA abnormalities during tumor proliferation. intratumoral heterogeneity; cytofluorometry; immunohistochemistry; esophageal carcinoma With the aid of flow cytometry and cytofluorometry, the determination of the DNA content in various types of tumors (Sannohe and Hiratsuka 1981;Sugimachi et al. 1986;Heikki et al. 1990;Sing et al. 1990;Fujimoto et al. 1991) has been widely carried out to evaluate the degree of malignancy and prognosis. Compared with the flow cytometry, the cytofluorometry has been reported to have more advantage to measure the DNA content in specific target cells and to provide more accurate results from small tissue samples (Cusic et al. 1990). The cytofluorometric study has drawn out the concept of tumor cell heterogeneity from the finding that intratumor variation exists in DNA content in malignant tumors of kidney (Ljungberg et al. 1985), colon (Quirke et al. 1985) and lung (Carey et al. 1990). The biological and clinical significance of tumor cell heterogeneity, however, has been not well recognized especially in esophageal cancer which has been reported to possess more different malignant potentiality than other malignant tumors (Matsumura et al. 1986;Kaketani et al. 1989; Robaszkiewicz et al. 1991). On the other hand, recent immunohistochemical studies have indicated that the autocrine secretion of epidermal growth factor (EGF) is responsible for tumor growth of several organs (Ikeuchi et al. 1987;Sugiyama et al. 1989;Asamoto et al. 1990;Mukaida et al. 1991). From these considerations, we undertook an investigation into the amount of nuclear DNA, and the expression of EGF and EGF-receptor (EGF-R) to clarify the clinical significance of these factors in esophageal cancer. MATERIALS AND METHODSSurgically extirpated specimens were obtained from 23 primary esophageal squamous cell carcinoma cases (Table 1). T...

A systematic review and meta-analysis of somatic and germline DNA sequence biomarkers of esophageal cancer survival, therapy response and stage

“…Following exclusion of one study including intratumoral heterogeneous ploidy [ 93 ] an association with worse OS was demonstrated [HR 1.63 (1.25–2.11); n = 4; P = 0.2 × 10 −4 ]. One study assessed intratumoral heterogeneity alone, reporting better survival than with homogeneity [ 94 ]. There were no associations between MSI and survival.…”