p53 mutational spectrum of esophageal carcinomas from five different geographical locales in China.

A mutational spectrum for exons 5-8 of the p53 tumor suppressor gene in esophageal carcinomas in mainland China and Hong Kong was established. This study involved 209 squamous cell carcinoma specimens obtained from five different geographical locales in China: Zhengzhou, Taiyuan, Shantou, Guangzhou, and Hong Kong. Zhengzhou and Shantou were high-incidence regions for esophageal cancer, whereas the other three regions had low or intermediate incidence of the disease. Analysis by single-strand conformation polymorphism and DNA sequencing showed that 87 specimens (41.6%) contained mutations in exons 5-8 of the p53 gene compared to 163 cases (78%) that had accumulation or aberrant expression of the protein, as detected by immunohistochemical staining. Point mutations accounted for 80.4% (87/107) of all genetic changes. The specimens from northern China exhibited fewer p53 gene aberrations and a more even distribution of mutations in exons 5-8 compared to those from southern China in which 60% of all mutations were found in exon 5. A major hot spot was found at codon 176 in exon 5, where 41 samples from Shantou, Guangzhou, and Hong Kong had a G-->T transversion. It is likely that among southern Chinese this codon is susceptible to mutagenesis by carcinogens. Codons 175, 203, 245, 250, 273, and 282 were also shown to be mutational hot spots, with three or more mutations observed at each site. The p53 mutational data obtained in this study showed that Chinese esophageal carcinomas are often associated with some unique genetic alterations, which may be attributed to specific dietary or environmental carcinogens that affect the Chinese but not Caucasians.

Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the lung in southern China.

Having reviewed the data on 3,663 consecutive cases of primary lung carcinoma in southern China, we found that 32 cases could meet the criteria for lymphoepithelioma-like carcinoma (LELC) of the lung. To study the relationship between pulmonary LELC and Epstein-Barr virus (EBV) infection, we used in situ hybridization and immunohistochemistry techniques to detect the EBV-encoded small nonpolyadenylated RNA (EBER), latent membrane protein 1 (LMP1), and viral capsid antigen (VCA) in 32 cases of LELC and 19 cases of non-LELC lung carcinoma. Of the 32 cases, 30 (94%) showed EBER positivity. Of the 30 EBER-positive pulmonary LELC cases, 16 and 7 expressed LMP1 and VCA, respectively. In contrast with LELC, none of the 19 cases of non-LELC lung carcinoma showed EBER-, LMP1-, or VCA-positive signals in carcinoma cells. The results demonstrate that there is a close relationship between EBV infection and pulmonary LELC. EBV infection may have an essential role in the tumorigenesis of pulmonary LELC. EBV latent infection is the main status in pulmonary LELC except for individual EBV entering into a lytic cycle.

A morphologic and follow-up study on the nasopharyngeal lymphoid hyperplasia and its relation to the cancer.

Fourty-three cases of nasopharyngeal lymphoid hyperplasia (NPLH) were studied morphologically and by follow-up during a period of 8.5 years in a high-incidence city of nasopharyngeal carcinoma (NPC). The authors suggest that NPLH might be recognized as a disease entity in adults. Based on the sites and gross appearances of the hyperplastic lymphoid tissue, two types of NPLH, namely, adenoids and nodular, could be distinguished. The histopathological changes of NPLH were described in detail, and its relation to the development of NPC was discussed. According to this study, the authors disagree with the opinion that NPLH is a precancerous lesion.

[DNA content and its distribution pattern of poorly differentiated nasopharyngeal carcinoma measured by Feulgen cytophotometry].

Nuclear area and DNA content of the normal columnar cells and cancer cells which were small, fusiform, irregular, vesicular-nuclear, giant malformed-nuclear and giant vesicular-nuclear were measured by Leitz MPV-III microscope photometer with HP-85 microcomputer in 32 poorly differentiated nasopharyngeal carcinoma (NPC) and 5 chronic nasopharyngitis sections. Based on different DNA contents and distribution patterns, it was divided into 4 cancer cell populations: small, fusiform and/or irregular, vesicular-nuclear and giant tumor cell populations. It should be noted that the nuclear DNA pattern of vesicular-nuclear cancer cell population had pathognomonic characteristics. The nuclear unit DNA content ratio of vesicular-nuclear cancer cells to lymphocytes was under 0.4. This cancer cell population was sensitive to irradiation. If the biological characteristics of these four cancer cell populations could be clarified not only in nuclear DNA pattern but also in biochemistry at molecular level, it will be possible to design the different treatment trials on the different cancer cell populations, then resulting in better prognosis of NPC patients.

[Morphometric study on nasopharyngeal carcinoma (NPC)].

Morphometric parameters of carcinoma cells in 78 NPC and columnar epithelium basal cells in 21 of these 78 NPCs were measured by Quantimet 520 analyser. The results showed that: 1. Prominent enlargement of nuclei was a pathognomonic feature of carcinoma cells, except small spindle carcinoma cells, as compared with the normal basal cells, 2. vesicular nucleus cell carcinoma and small spindle poorly differentiated squamous carcinoma had their own characteristic morphometric parameters as compared with those of the ordinary poorly differentiated squamous carcinoma, and 3. there was no significant morphometric difference between vesicular nucleus cell carcinoma and poorly differentiated adenocarcinoma.

[Nasopharyngeal carcinoma (NPC) mortality rate in two districts of Guangdong Province and their relation to IgA antibody level against EB virus capsid antigen].

Based upon the retrospective investigation data, the NPC mortality rate in the Pearl River Delta was found to be twice as high as that of Chaoshan district. The positive rate of IgA/VCA antibody in the Pearl River Delta was also found to be significantly higher than that in the Chaoshan district by viro-serological screening. The IgA/VCA antibody positive rate and mortality rate were concomitantly increased with age in the bracket of 30-59. Accordingly, the authors assume that activation of infected EB virus might be an important factor in the process of etiology-pathogenesis of NPC.

[In situ lesion of para-nasopharyngeal carcinoma--microspectrophotometer study].

Eighteen tissue sections of in situ cancer of para-nasopharyngeal carcinoma (NPCIS) were assayed for nuclear area, DNA content, nucleolar area and RNA content using MPV III microspectrophotometer. In general, the nuclear area, DNA content, nucleolar area and RNA content in NPCIS cells were significantly increased as compared with those in the non-cancerous epithelial cells. The DNA-histogram showed aneuploidy in the majority of NPCIS. In the invasive carcinoma foci, the above-mentioned characteristics were more marked. The authors believe that NPCIS is a critical stage in the pathogenesis of NPC. In addition, the comparison is described as to the similarities and differences between the columnar and squamous cell types of NPCIS.

[A morphologic and follow-up study on nasopharyngeal lymphoid hyperplasia and its relation to cancer].

Forty-three cases of nasopharyngeal lymphoid hyperplasia (NPLH) were studied morphologically and had been followed-up for a period of 7.5 years in a high-incidence city of nasopharyngeal carcinoma (NPC). The authors suggest that NPLH might be recognized as a disease entity in adults. Basing on the sites and gross appearances of the hyperplastic lymphoid tissue, two types of NPLH, namely, adenoids and nodular might be distinguished. The histopathological changes of NPLH are described in detail and its relation to the development of NPC is discussed. According to the data of this study, the authors' opinion is that NPLH is not a precancerous condition.

[Study on the role of EB virus in carcinogenesis of nasopharyngeal carcinoma by use of in situ hybridization].

Cryosections of 45 nasopharyngeal carcinomas and 9 non-tumorous biopsies were studied for EBV DNA by use of in situ hybridization. No EBV DNA was detected in all types of non-epithelial cells. One to three copies of EBV genome as shown by Namalwa cells could occasionally be found in a small number of normal, hyperplastic, squamously metaplastic and dysplastic epithelial cells. A considerable number of neoplastic cells in 6 para-tumourous carcinoma in situ foci contained numerous EBV genome copies as shown by Raji cells. The majority of infiltrating cancer cells of 42 non-keratinizing carcinomas and 3 keratinizing squamous cell carcinomas also exhibited quite a number of EBV genome copies. The above findings illustrate that EBV may have a promotive effect during the early stage just after the malignant conversion of epithelial cells to increase the proliferative rate of carcinoma cells.