Journal of Pathology and Translational Medicine

Volume 37(2); April 2003

Original Articles

Expression of Hypoxia-inducible Factor-1 alpha Protein in Stages I and II Squamous Cell Carcinomas of the Uterine Cervix: Relationship with p53 Protein and VEGF Expressions.: Dong Soo Suh, Chang Hun Lee, Kang Suek Suh, Man Soo Yoon; Korean J Pathol. 2003;37(2):79-86.

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Abstract PDF: BACKGROUND
Under hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) is known to activate the expression of various genes, including angiogenesis-related genes. The aim of this study was to evaluate the expression of HIF-1alpha protein and its relationship with p53 protein expression and angiogenesis in the squamous cell carcinoma (SCC) of the uterine cervix.
METHODS
Using immunohistochemical methods, the expression of HIF-1alpha protein, p53 protein, vascular endothelial growth factor (VEGF), and microvessel count were evaluated in seventy cases of FIGO stages I and II SCC; and their results were compared with age, stage, and pelvic lymph node metastasis.
RESULTS
Positive nuclear staining for HIF-1alpha protein was noted in 19 cases (27.1%). Carcinoma in situ or dysplastic lesions also revealed positive nuclear reaction along the lower part of the epithelium. The expression of HIF-1alpha protein was significantly related with those of p53 protein and VEGF (p<0.05), but not with other clinicopathologic parameters. The microvessel count showed a significant difference regarding stage and VEGF expression (pand<0.05).
CONCLUSION
These findings suggest that HIF-1alpha expression in SCCs of the uterine cervix might be the early event of carcinogenesis and could be associated with p53 protein and VEGF expression. However, the prognostic significance of HIF-1alpha expression in stages I and II SCCs is undetermined.

Alveolar Soft Part Sarcoma of the Lung: A Report of Six Cases and Clinicopathological Analysis.: Na Rae Kim, Mi Sook Lee, Young Cheol Yoon, Dae Su Kim, Kyong Soo Lee, Gee Young Suh, Jhingook Kim, Joung Ho Han; Korean J Pathol. 2003;37(2):87-92.

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Abstract PDF: BACKGROUND
Alveolar soft part sarcoma (ASPS) accounts for 0.5-1% of soft tissue sarcomas, and often metastasizes to the lung. Cases of pulmonary ASPS of unknown primary site have rarely been reported in literature.
METHODS
Here, we report three cases of metastatic pulmonary ASPS and three cases of presumably primary ASPS using immunohistochemistry and clinicoradiologic findings.
RESULTS
All of the cases occurred in young females. Two of the cases had metastasized from soft tissue ASPS of the lower extremities, and one case had metastasized from one of the patient? femur bones. Immunohistochemical stains were applied to four cases that had available paraffin blocks. The tumor cells of all cases on which immunohistochemical stains were done were positive for vimentin (4/4, 100%). None of the tumors were positive for myoglobin, desmin, smooth muscle actin, progesterone receptor, estrogen receptor, thyroid transcription factor-1, S-100 protein, pancytokeratin, and HMB-45 antibodies.
CONCLUSION
The present study revealed that the rare pulmonary ASPS has nonspecific clinicoradiologic findings. In the immunohistochemical results, no differences existed between the presumably primary ASPS and the metastatic ASPS except for a higher Ki-67 labeling index in the latter (less than 0.1% vs. 30%). The higher index was not dissimilar to those of the extrapulmonary ASPS which showed a tumor with a low proliferation index, signifying a better prognosis and have a low potential to metastasize.

Smad4 Expression in Gastric Adenocarcinoma.: Hyeon Ok Kim, Do Youn Park, Kang Suek Suh; Korean J Pathol. 2003;37(2):93-99.

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Abstract PDF: BACKGROUND
The role of Smad4 in carcinogenesis is important, because of its function as a central mediator of TGF-beta signaling. In the present study we analyzed the expressions of Smad4 mRNA and protein in human gastric cancer cell lines and tissues and we also analyzed their clinicopathological significance.
METHODS
We used semi-quantitative RT-PCR for Smad4 mRNA expression in 13 cases of fresh gastric cancer tissues and two gastric cancer cell lines (MKN-28, SNU-1). We also used immunohistochemistry for Smad4 protein expression in 88 cases of formalin fixed gastric cancers tissues.
RESULTS
The mRNA level of Smad4 was higher in MKN-28 cell line (intestinal type) than in the SNU-1 cell line (diffuse type). Fresh frozen gastric cancer tissues showed that the intestinal type of gastric cancer had higher Smad4 mRNA expressions than the diffuse type of gastric cancer (p<0.05). Immunohistochemical staining for Smad4 revealed that cytoplasmic and nuclear expressions of Smad4 were significantly correlated with histologic types of gastric cancer (p<0.05). That is, the intestinal type of gastric cancer showed more cytoplasmic and nuclear smad4 expressions than did the diffuse type of gastric cancer. Reduced cytoplasmic expressions and positive nuclear expressions of Smad4 were more prominent in the advanced gastric cancer than in the early gastric cancer.
CONCLUSION
Taken together, we suggest that loss of Smad4 expression might be associated with the intestinal type of gastric cancer. Also reduced cytoplasmic Smad4 expressions and increased nuclear Smad4 expressions may be associated with the advanced stage of gastric cancer.

Expression of p63 in Lung Cancer.: Sungjig Lim, Jung Yeon Kim, Kyeougmee Park; Korean J Pathol. 2003;37(2):100-107.

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Abstract PDF: BACKGROUND
The DNA-binding protein p63, a member of the p53 family, regulates differentiation and proliferation of epithelial progenitor cells. In this study, we evaluated the expression of p63 in lung cancer to gain insight into the pathogenesis of these processes.
METHODS
A total of 89 patients who had undergone potentially curative surgery for lung cancer were selected. Expressions of p53, p63, and deltaNp63 were analyzed immunohistologically using a tissue array method with formalin-fixed, paraffin-embedded specimens. Immunohistological results were then correlated with clinicopathological parameters with prognostic implications.
RESULTS
Expressions of p63 and deltaNp63 were found in 47 (52.8%) and 38 (43.2%) of the 89 patients, respectively. No relationships between the p63 or deltaNp63 expressions and any clinicopathological variables were found. p63 was expressed in 92.5% (37/40) of the squamous cell carcinomas, 17.9% (7/39) of the adenocarcinomas, 20% (1/5) of the small cell carcinomas, and 0% (0/5) of the large cell carcinomas. deltaNp63 was expressed in 92.3% (36/39) of the squamous cell carcinomas, 2.5% (1/39) of the adenocarcinomas, 0% (0/5) of the small cell carcinomas, 0% (0/5) of the large cell carcinomas, and 50% (1/2) of the adenosquamous cell carcinomas. In the squamous cell carcinomas, significantly high expressions of p63 and deltaNp63 were found (p<0.05). p53 protein was detected in samples from 49 of the 89 patients (55.1%). No significant associations between the p53 expressions and the p63 or deltaNp63 expressions were noted.
CONCLUSION
p63 or deltaNp63 is likely to be involved in the development of squamous cell carcinomas of the lung and no significant association was found between p63 or deltaNp63 and patient survival rates.

Expression of Transforming Growth Factor-beta and Its Receptors during Acetic Acid-induced Duodenal Ulcer Healing in Rats.: Kyu Yun Jang, Han Sang Yoon, Ki Hoon Yu, Myung Ja Chung, Dong Geun Lee, Jae Kang Myoung; Korean J Pathol. 2003;37(2):108-114.

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Abstract PDF: BACKGROUND
Many works have been written about the transforming growth factor-beta 1 (TGF-beta1) which is closely associated with fibrosis in the inflammatory conditions of different organs. TGF-beta1 exerts its biological effects by interacting with specific cell surface receptors, namely, transforming growth factor-beta receptor type I and II (TGFbetaRI and TGFbetaRII).
METHODS
To investigate the temporal expressions and localizations of TGF-beta1, TGFRbetaI, and TGFbetaRII in acetic acid-induced duodenal ulcerated tissues, we performed in situ hybridization and immunohistochemical techniques.
RESULTS
Under in situ hybridization, TGF-beta1, TGFbetaRI, and TGFbetaRII mRNA signals increased in the experimental groups (1, 3, 7, and 14 day groups) compared to those of the control group. The signals on day 14 decreased slightly compared to those of days 1, 3, and 7, but they were higher than those of the control group. Under immunohistochemical study, TGF-beta1, TGFbetaRI, and TGFbetaRII were localized in the mucosal epithelial cells and in the macrophages, vascular endothelial cells, and fibroblasts of the lamina propria and granulation tissue. As in the case of the in situ hybridization, it revealed that the expression of three proteins increased in the experimental groups compared to that of the control group. The expression on day 14 decreased compared to those of days 1, 3, and 7, but it was more intense than that of the control group.
CONCLUSIONS
This study suggests that TGF-beta1, TGFbetaRI, and TGFbetaRII contribute to the early stage healing of duodenal ulcer.

Quantitative Nuclear Characteristics of Lung Cancer Cells Using Image Analysis.: Moon Kyoung Kim, Chung Yeul Kim, Woon Yong Jeong, Ji Hye Lee, Eung Seok Lee, Seung Yeon Ha, Young Sik Kim, Han Kyeom Kim, In Sun Kim; Korean J Pathol. 2003;37(2):115-120.

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Abstract PDF: BACKGROUND
The usefulness of quantitative nuclear image analysis in the classification of lung carcinoma is widely investigated and published. In this study, we tried to measure the nuclear characteristics of primary lung carcinomas by image analysis and to find the possibility of differential diagnoses.
METHODS
Seventeen cases of adenocarcinomas (not including bronchioloalveolar carcinoma), seven of bronchioloalveolar carcinomas, eight of large cell neuroendocrine carcinomas, five of small cell carcinamas, and 26 of squamous cell carcinomas were analysed. Three different images of each case were captured by digital camera, and we analyzed the nuclear area, perimeter, circularity, and density using the Optimas 6.5 Image Analyser software package. Statistical analyses were done using the statistical program STATISTICA kernel release 5.5.
RESULTS
The mean nuclear area was 0.52+/-0.25micrometer2 in the adenocarcinomas, 0.50+/-1.82micrometer2 in the squamous cell carcinomas, 0.45+/-0.20micrometer2 in the large cell neuroendocrine carcinomas, 0.42+/-0.16micrometer2 in the bronchioloalveolar carcinomas, and 0.31+/-0.12micrometer2 in the small cell carcinamas. The nuclear area was significantly different between the small cell carcinomas and the non-small cell carcinomas (p<0.01) and between the adenocarcinomas and the bronchioloalveolar carcinomas (p=0.02). The mean nuclear perimeter was 3.36+/-0.92micrometer2 in the adenocarcinomas, 3.24+/-0.67micrometer2 in the squamous cell carcinomas, 3.16+/-0.82micrometer2 in the large cell neuroendocrine carcinomas, 3.05+/-0.80micrometer2 in the bronchioloalveolar carcinomas, and 2.54+/-0.62micrometer2 in the small cell carcinamas. The nuclear perimeter was significantly different between the small cell carcinomas and the non-small cell carcinomas (p<0.04). The nuclear circularity showed no statistical difference. Nuclear density was the highest in the squamous cell carcinomas, and the lowest in the small cell carcinomas. The large cell neuroendocrine carcinomas showed the lowest standard deviation in nuclear density.
CONCLUSION
The analysis of nuclear characteristics using an image analyser can be used as an objective method in the classification of lung carcinoma.

Expression of TGF-beta1 and TGF-betatype II Receptor in Chemically Induced Hepatocarcinogenesis of the Rat.: Do Youn Park, Kang Woo Park, Kang Suek Suh; Korean J Pathol. 2003;37(2):121-128.

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Abstract PDF: BACKGROUND
Transforming growth factor (TGF)-beta1 inhibits hepatocyte proliferation by inducing apoptosis. Expression of TGF-beta1 is tightly associated with the TGF-betatype II receptor (TGR2) expression level, and has been regarded as an important change of TGF-beta1 and TGR2 during hepatocarcinogenesis. We investigated the gene expressions and protein localizations of TGF-beta1 and TGR2 in chemical hepatocarcinogenesis.
METHODS
Solt and Farber's method was used as the chemical hepatocarcinogenesis model of the rat. Northern blot analyses and immunohistochemistry for TGF-beta1 and TGR2 were performed to investigate the gene expressions and protein localizations, respectively.
RESULTS
The Northern blot analyses showed a slight increase of TGF-beta1 transcripts one month after partial hepatectomy, which is more than in sham operated control liver, and a decrease of transcripts for TGR2 two months after partial hepatectomy. The number of TGF-beta-positive preneoplastic hepatocytes was increased and correlated with the increase of the number of TGR2 negative hepatocytes or reduction of expressions of TGR2 in preneoplastic lesions. HCC tissues showed an increase of TGF-beta1 protein expressions and a decrease of TGR2 compared to the adjacent liver parenchyme.
CONCLUSION
Our data suggest that down regulation of TGR2 in preneoplastic lesions and HCC might contribute to the resistance to the growth inhibitory effects of TGF-beta.

Case Reports

Cerebral Amyloid Angiopathy: A Case Report.: Na Rae Kim, Jae Gul Chung, Sang Koo Lee; Korean J Pathol. 2003;37(2):129-133.

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Abstract PDF: Symptomatic cerebral amyloid angiopathy (CAA) is characterized by lobar cerebral hemorrhage, transient neurological symptoms, and dementia with leukoencephalopathy in the absence of hypertension or coagulopathy. Contrary to its common appearance in English literature, pathologically confirmed CAA has rarely been reported in Korea. A 77-year-old normotensive, nondemented woman was admitted for a case of incidentally found intracerebral lobar hemorrhage at the left occipito-parietal area. On neurological examination, she displayed symptoms of a drowsy mentality and Gerstmann syndrome. Light-microscopically, medium to large cortical and meningeal vessels appeared to be thickened with amorphous glassy materials showing apple-green birefringence under polarized light on Congo red stain, which is consistent with CAA. The amyloid deposits were detected in the medium-sized vessels of the leptomeninges and cerebral cortex, but not in the capillaries and small arterioles in the white matter. Electron microscopy revealed amyloid fibrils and basal lamina duplication, indicating damaged vessels. Careful cortical biopsy during evacuating hematoma for histopathologic and ultrastructural examination is essential for diagnosis of CAA in case of clinical probability because the ignored sampling procedure and sampling error of patchy, segmental distribution of affected vessels might be ascribed to rare incidence of CAA in Korea.

Cystic Adenomyoepithelioma of the Breast: A Case Report.: Ji Shin Lee, Myung Sook Choi; Korean J Pathol. 2003;37(2):134-136.

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Abstract PDF: Adenomyoepithelioma of the female breast is a rare tumor. With rare exceptions, the tumor is uniformly solid. We describe a large grossly cystic adenomyoepithelioma in a 67-year-old female. The tumor was histologically benign. The characteristic microscopic finding was the proliferation of rounded tubules lined by both epithelial and myoepithelial cells. Immunohistochemical findings confirmed the presence of two cell population.

Solitary Fibrous Tumor of Meninges in Pituitary Fossa: A Case Report.: Dae Woon Eom, Shin Kwang Khang, Chang Jin Kim, Jae Y Ro; Korean J Pathol. 2003;37(2):137-140.

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Abstract PDF: Solitary fibrous tumor (SFT) was originally described in the pleura. An increased number of extrapulmonary sites of SFTs has been described. We report a case of SFT of the meninges in the pituitary fossa. A 56-year-old man was admitted with a severe headache and visual disturbance. The tumor, with osteolytic bony change, was 3.5 cm in greatest dimension and extended from the sphenoid sinus to the third ventricle level. Histologically, the tumor showed the typical features of a solitary fibrous tumor with no evidence of being high grade. By immunohistochemical study, the tumor cells were positive for CD34, vimentin, and Bcl2, but were negative for epithelial membrane antigen and S-100 protein. When fibrous tumors or tumors with hemangiopericytic vascular pattern involve the meninges, the possibility of their being SFTs should be considered, and a proper immunostaining is recommended. To our knowledge, ours is the first description of a case of SFT occurring at the meninges in the pituitary fossa.

Primary Adenocarcinoma of the Seminal Vesicle: A Case Report.: Eundeok Chang, Anhi Lee, Jehoon Lee, Eunjung Lee, Changsuk Kang; Korean J Pathol. 2003;37(2):141-144.

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Abstract PDF: Primary adenocarcinoma of the seminal vesicle is an extremely rare tumor, and its prognosis has been known to be poor. Herein, we report an adenocarcinoma of the seminal vesicle. The patient was a 50-year-old man who complained of a two-month history of terminal hematuria and lower abdominal discomfort. A pelvic magnetic resonance imaging study. Indicated a seminal vesicle cyst with focal intraluminal growth. Right seminal vesiculectomy was performed. Grossly, the seminal vesicle revealed a markedly cystic change with focal, friable, intraluminal papillary growth. The intraluminal mass showed a noninvasive adenocarcinoma with a tubular and tubulopapillary pattern, accompanied by necrosis. Immunohistochemically, the tumor was positive for cytokeratin and carcinoembryonic antigen and negative for prostate specific antigen and prostatic acid phosphatase.

Primary Primitive Neuroectodermal Tumor of the Kidney: Report of Two Cases.: Hyun Lyoung Koo, Sun Young Jun, Gene Choi, Jae Y Ro, Hanjong Ahn, Kyung Ja Cho; Korean J Pathol. 2003;37(2):145-149.

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Abstract PDF: Primitive neuroectodermal tumor (PNET) is a small round cell neoplasm that mainly develops in the central nervous system and soft tissue of children. Primary occurrence in the kidney is rare and the identification of immunopositivity for CD99 and t(11;22)(q24;q12) is essential in differential diagnoses. We report two cases of PNET developed in a 21-year-old woman and a 44-year-old man. Resected tumors were composed of sheets of round or ovoid cells with hyperchromatic nuclei and minimal eosinophilic cytoplasm. Rosette formations, more prominent in the first case, were observed. The tumor cells of both cases were diffusely positive for CD99, vimentin, and neuron specific enolase, while they were negative for cytokeratin, desmin, and chromogranin. Synaptophysin was focally expressed only in the first case. The EWS-FLI1 chimeric gene was identified by a reverse transcriptase-polymerase chain reaction in the first case. The first patient is alive with a recurrent tumor two years after the diagnosis, and has received combination chemotherapy. The second patient is alive with no evidence of recurrence or metastasis nineteen months after the diagnosis.

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