Journal of Pathology and Translational Medicine

Original Articles

Telomerase Activity in Urethane-Induced Mouse Lung Tumorigenesis.: Ji Sun Song, Soon Hee Jung, Sang Yeop Yi, Hwa Eun Oh, Mee Yon Cho, Kwang Hwa Park; Korean J Pathol. 2011;45(3):261-270.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.261

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BACKGROUND
Telomerase activity in precancerous conditions of lung adenocarcinomas has not been well studied. This study is designed to investigate the role of telomerase in premalignant lesions of urethane-induced mouse lung adenocarcinoma.
METHODS
We harvested A/J mouse lung tissues at 3, 6, 9, 12, 28, 41, and 48 weeks after intraperitoneal urethane treatment, and classified each lesion in terms of histologic findings. We examined telomerase activity using a modified version of the telomeric repeat amplification protocol assay using both gel-based and enzyme linked immunosorbent assay methods. An immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) was performed.
RESULTS
In urethane-induced mouse lung tissues, it was sequentially developed from hyperplasia, adenoma, and eventually to adenocarcinoma. Telomerase activity began to show a positive level in tissues with no histologically visible nodule after urethane administration. It revealed a statistically significant increase in hyperplasia compared to the "control" lung tissue (p<0.05), which was proportionally elevated relative to adenoma and adenocarcinoma. There was a direct correlation between telomerase activity and the PCNA labeling index (p<0.05).
CONCLUSIONS
The elevation of telomerase activity in normal-appearing lung lesions is thought to be a possible marker of early detection of pulmonary adenocarcinoma.

Citations

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Non-invasive quantification of cell-free DNA mutations in plasma during lung tumor progression in mice
Soo-Jin Kim, Eunhee Kim, Kyung-Taek Rim
Cancer Biomarkers.2017; 20(4): 477. CrossRef

Immunohistochemical Study of the Expression of p53, Pan-ras, c-erbB-2 and PCNA in N-Nitrosomorpholine(NNM)-Induced Hepatocellular Carcinoma of Rats.: Ok Kyung Kim, Ryun Jo Shin; Korean J Pathol. 1995;29(6):727-739.

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Abstract PDF: The focus of this study was o aialyze the morphologic expression of p53, Pan-ras, c-erbB-2, and PCNA in preneoplastic and neoplastic liver lesions induced with NNM of rats. The development of hepatocellular tumors was investigated by histology and electron microscope in 65 Splague-Dawley rats administered with NNM in drinking water at low dose(5 mg/100 ml) and high dose(20 mg/100 ml). Three types of hepatocytic degeneration glycogenotic, eosinophilic and basophilic changes were followed by the appearance of hepatocellullar carcinoma. Hepatocellular carcinoma was increased in number and size according to NNM dosage and to duration of exposure. The histological classifications of hepatocelular carcinoma wer trabecular type, which was which was the most common, large eosinophilic, small cell, adenocarcinomatous and clear cell type. The expression of p53, Pan-ras, c-erbB-2 PCNA was examined by immunohistochemical stains. Eosinophilic degeneration revealed mild positivity at 18-26 weeks for expression of all oncogenic proteins studied and PCNA, whereas precancerous lesions showed variable expression from negative to moderate positivity on PCNA. Hepatocellular carcinoma lesions showed strong positivity for all stains and increased intensity during experimental period. These may indicate that chemical carcinogen produce hepatic eosinophilic degeneration and preCancerOus lesions by genetic mutation, resulting in hepatocellular carcinoma.

Assay of Proliferative Activity, Clonality and Immortality of.: Hyung Seok Kim, Young Jik Lee, Mee Sook Kim, Hyang Mi Ko, Sang Woo Juhng; Korean J Pathol. 1999;33(9):652-661.

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Abstract PDF: Among the precancerous lesions, dysplasia of the uterine cervix and adenoma of the colon have been widely studied in terms of genetic alterations. However, little has been performed regarding phenotypic alterations of the precancerous lesions. We investigated the relationship among cellular proliferation, clonality, immortality and histopathologic grading of the squamous epithelial lesions of the uterine cervix. Proliferation index (PI) was calculated based on the ratio of the epithelial cells positive for proliferating cell nuclear antigen to the total epithelial cells. Clonality was assayed by X-linked HUMARA polymorphism. For immortality assay, PCR-based TRAP (telomeric repeat amplification protocol) was done and telomerase processivity was calculated by comparison with the positive control. PI increased gradually as the lesions advanced from dysplasia to invasive carcinoma. Among informative case, all of the carcinoma in situ showed monoclonal pattern (7 of 7). Among invasive squamous cell carcinoma, 6 cases showed monoclonal pattern and 2 cases polyclonal pattern. TRAP reaction was positive in 92.6% (25 of 27) of dysplasia (high grade: 14 of 15; low grade: 11 of 12), 95.0% (19 of 20) of carcinoma in situ, 100% (9 of 9) of microinvasive carcinoma, and 92.9% (13 of 14) of invasive carcinoma. It was also positive in 12 of 12 samples of chronic cervicitis or squamous metaplasia near the lesions of dysplasia. There was no difference in TRAP positivity among the dysplasia, carcinoma in situ and invasive carcinoma, whereas telomerase processivity showed significant correlation. These results suggest that proliferative activity and telomerase processivity may be progressive events in oncogenesis, although telomerase activation may be an early event.

Expression of bcl-2 and p53 Protein in Premalignant Lesion and Invasive Squamous Cell Carcinoma of the Uterine Cervix.: Hyun Chang Joo, Kwan Kyu Park, Sang Sook Lee, Eun Sook Chang, Tae Sung Lee, Soon Do Cha, Young Jae Lee; Korean J Pathol. 2000;34(4):280-287.

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Abstract PDF: In order to understand the possible involvement of bcl-2 and p53 proteins in the tumorigenesis of the cervical cancer and precancerous lesion, we studied the expression patterns of bcl-2 and p53 proteins in 25 cases of carcinoma in situ, 12 cases of microinvasive cervical carcinoma, and 37 cases of invasive cervical carcinoma, respectively. By immunohistochemistry, 76% of in situ carcinoma, 83.3% of microinvasive cervical carcinoma, and 60.9% of invasive cervical carcinoma were positive for bcl-2, while the staining of basal cell layers, columnar cells, and squamous metaplastic epithelium of normal cervical epithelium were positive for bcl-2 in 91.9%, 73.1%, and 81.8% of cases, respectively. Furthermore, two out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for bcl-2. p53 was expressed in 72.7% of condyloma or dysplasia, 12% of in situ carcinomas, 33.3% of microinvasive cervical carcinoma, and 43.5% of invasive cervical carcinomas without metastasis. Six out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for p53 immunostaining. In contrast, 5.4% of basal cells and 9.1% of squamous epithelium, and none of the columnar cells in normal cervical epithelium were positive for p53. In summary, the bcl-2 protein was highly expressed in the proliferative lesion of reserve cells, such as normal reserve cells, columnar cells, squamous metaplasia, carcinoma in situ, and microinvasive squamous cell carcinoma. p53 expression was increased in condyloma, carcinoma in situ, and invasive carcinoma where the reserve cells were non-proliferative. Based on these findings, we propose that bcl-2 and p53 protein are involved in the development and progression of uterine cervical carcinoma.

A Study on the Precancerous Lesion of Breast Carcinoma in 9, 10-Dimethyl-1, 2-Benzanthracene-treated Rats.: Cheon Sik Choi, Soo Min Kang, Hye Jung Lee, Gyung Hyuck Ko, Cheol Keun Park; Korean J Pathol. 1991;25(2):104-113.

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Abstract PDF: Following results were obtained from the light microscopic and stereomicroscopic observations of the breasts of rats treated with 9, 10-Dimethyl-1,2-Benzanthracene(DMBA). 1) Adenocarcinomas developed in 17 rats (24%) among 70 DMBA-treated rats. 2) Terminal and buds (TEB) were observed longer in DMBA-treated rats than in control group, but they finally disppeared 4 monthes after treatment. 3) Many hyperplastic alveolar nodules (HAN) developed in DMBA-treated rats. 4) There were no transitional lesions between TEB and adenocarcinoma or HAN and adenocarcinoma. 5) The number of lobules was decreased in DMBA-treated rats. On the other hand, terminal ducts were increased in number. These findings suggest that DMBA stimulate the regression of lobules and induce to form terminal ducts from which adenocarcinomas and HAN develop independently.

Case Report

Hyperkeratosis of Renal Pelvis and Ureter: A case report.: Mi Kyung Lee, Hyeon Joo Jeong, In Joon Choi; Korean J Pathol. 1987;21(4):298-302.

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Abstract PDF: Hyperkeratosis of the renal pelvis and ureter is a rare condition and is explained by the metaplastic change from transitional to cornified squamous epithelium. This lesion is frequently associated with, and perhaps caused by chronic urinary infection, but potentially premalignant, accompaning with carcinoma in about 10 to 20 per cent of the cases at the time of diagnosis. A case of hyperkeratosis of renal pelvis & ureter which was clinically suspected of carcinoma in a 49-year old woman with a long history of chronic pyelonephritis is presented with review of literature.

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