Journal of Pathology and Translational Medicine

Volume 31(6); June 1997

Original Articles

Expression of p53 and nm23 Proteins in Non-Small Cell Lung Cancer.: Mi Seon Kwon, Won Il Kim, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1997;31(6):499-507.

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Abstract PDF: To elucidate the role of p53 and nm23 in the development, progression, and metastasis of non-small cell lung cancer, we studied 91 paraffin sections of the primary non-small-cell lung cancers and the 34 paraffin sections of their metastatic lymph nodes using the immunohistochemical method. The results are as follows: 1) The incidence of p53 protein expression was positively correlated with the staging of lung cancers (p<0.025). 2) The incidence of p53 protein expression was higher in the lung cancers with lymph node metastasis than in those without lymph node metastasis (p=0.009). 3) The incidence of nm23 protein expression was lower in the adenocacinomas than in the squamous cell carcinomas (p=0.032). 4) The incidence of nm23 protein expression was lower in the lung cancers with lymph node metastasis than in those without lymph node metastasis (p=0.026). The expression of nm23 protein between the primary lung cancers and corresponding metastatic lymph nodes showed positive correlation (Kendall's Tau-b correlation coefficient=0.47140, p=0.0068). 5) The expression of p53 was not correlated with the expression of nm23 protein (Kendall's Tau-b correlation coefficient=0.11387, p=0.2800). The above results suggest that an overexpression of p53 protein and a downregulation of nm23 protein are associated with tumor progression and metastasis in non-small-cell lung cancer.

A Study on the Expression of p53 and nm23 Protein in the Colorectal Adenoma and Carcinoma.: Jin Hee Sohn, Eun Ha Jung, Hye Rim Park, Young Eui Park; Korean J Pathol. 1997;31(6):508-516.

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Abstract PDF: The expression of the nuclear phosphoprotein p53, a product of tumor suppressor gene, has been noted in a number of human tumors as a tumor suppressor. nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. To assess the role of p53 and nm23 expression in colorectal tumorigenesis and the association with clinicopathological parameters, an immunohistochemical study for mutant p53 and nm23 was done using mouse monoclonal antibodies in 43 colorectal carcinomas, 55 tubular adenomas and corresponding normal mucosa. In the tubular adenomas, p53 expression was significantly correlated with the degree of atypism(p<0.05) but not with other variables as well as with nm23. In the colorectal carcinoma, there were evidence of some correlation between metastasis, laterality and p53; laterality, depth of invasion and nm23 expression, but without statistical significance. Other clinicopathologic features were not significantly correlated. In the aspect of 'adenoma-carcinoma sequence', normal mucosa was totally negative for both p53 and nm23, and they were increasingly expressed through tubular adenoma to carcinoma with statistical significance(p<0.05). Therefore, it is suggested that both p53 and nm23 expressions occur in and around the time of transition to carcinoma from adenoma but are not significantly associated with the infiltrative behavior and metastasis.

Correlation between Tumor Angiogenesis (Microvessel Density), Metastasis and Tumor Cell Proliferation in Colorectal Carcinomas.: Young Chae Chu, Joon Mee Kim; Korean J Pathol. 1997;31(6):517-526.

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Abstract PDF: Tumor angiogenesis has been shown to be associated with metastatic potentials in breast, lung and prostatic carcinomas. The relation between tumor angiogenesis and metastatic potentials in colorectal cancer has not been established to date. We analysed 66 selected patients with colorectal carcinomas (37 with and 29 without nodal metastases) for the microvessel density, tumor proliferation activity, and the clinicopathologic parameters including size, stage, histologic grade, growth pattern, presence of angioinvasion, perineural invasion and lymph node metastasis. For evaluation of microvessel density and tumor proliferative activity, the primary tumors were immunohistochemically stained for CD31 and PCNA. The mean microvessel counts (MVC) per 200X field were 99.27+/-23.28 and 131.35+/-31.48 in node-negative and node-positive patients, respectively. The PCNA index was 39.41+/-5.63% and 56.60+/-7.09% in node-negative and node-positive patients, respectively. MVC and PCNA index were higher in tumors with nodal metastasis (p=0.002, p<0.001), and also correlated each other (sr=0.33, p=0.007). Higher microvessel counts were seen in tumors with advanced stage (p=0.016). Tumor proliferation activity assessed by PCNA immunostaining was significantly higher in tumors with advanced stage, perineural invasion, angioinvasion, poor differentiation and larger size. From these results, MVC and PCNA index in colorectal carcinomas are assumed to be valuable prognostic parameters. Thus assessment of tumor angiogenesis and tumor cell proliferation in colorectal carcinomas may be helpful for the patients in need of aggressive therapy.

Hyperplasia, Metaplasia, and Dysplasia of the Gallbladder Correlation to Gallbladder Adenocarcinoma.: Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(6):527-537.

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Abstract PDF: The correlation of metaplasia to dysplasia and carcinoma in the gallbladder has attracted the attention of many investigators. We mapped and examined a total of 263 cholecystectomized gallbladders to analyze the mucosal changes in the carcinogenesis of the gallbladder. Stones were present in 59.7%, hyperplasia in 28.5%, metaplasia in 55.5% (gastric 37.6%, intestinal 17.9%), dysplasia in 17.1% (low grade 9.1%, high grade 8%) and carcinoma in 7.6%. Metaplasia was more frequently identified in the stone-positive group (62.4%) than in the stone-negative group (45.3%) (P<0.05). Especially, the incidence of intestinal metaplasia was significantly higher in the stone-positive group. Dysplasia and carcinoma were more frequent in the metaplasia-positive group (dysplasia 26.7%, carcinoma 11%) than in the metaplasia-negative group (dysplasia 5.1%, carcinoma 3.4%) (P<0.05). Their incidences were significantly higher in the intestinal metaplasia than in the gastric metaplasia. Forty four percent of the dysplasia-positive cases were associated with carcinoma in the adjacent mucosa but carcinoma was absent in the dysplasia-negative cases. Hyperplasia did not reveal any significant correlation with metaplasia, dysplasia and carcinoma. These results suggest that gallstone is causally related to the metaplasia in the gallbladder and the metaplasia-dysplasia- carcinoma sequence exists in the gallbladder.

Expressions of the Tumor Associated Proteins and Their Correlation with the Pathologic Features in Childhood Hepatoblastoma.: Han Seong Kim, Hyo Seop Ahn, Kwi Won Park, Ja June Jang; Korean J Pathol. 1997;31(6):538-545.

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Abstract PDF: Hepatoblastoma is a rare malignant liver tumor found in children. Its biological characteristics and prognostic factors have not been well known. We investigated 29 cases of hepatoblastoma, registered in university hospitals in Seoul from 1984 to 1996. By the immunohistochemical method, p53, Waf-1 (p21), bcl-2, heat shock protein 70 (hsp70), c-jun, transforming growth factor-alpha (TGF-alpha) expressions were studied. Those data were compared with clinico-pathologic features; age, sex, tumor size, tumor stage and histologic subtypes. Expression of p53 and bcl-2 were each observed separately in single cases. Expression of c-jun was more frequently noted in patients at higher stages. Expression of TGF-alpha decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Cumulative survival rate was lower in females than in males and in patients with a higher tumor stage. According to histologic subtypes, survival rates decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Survival rate was lower in patients with c-jun expression. Group of TGF-alpha labelling index under 19 showed a lower survival rate than that over 19. In conclusion, we found that tumor associated proteins, c-jun and TGF-alpha, are closely related to the prognosis of hepatoblastoma but p53 and bcl-2 may not be related to it.

Expression of CD44 Splice Variants(v4/5 and v6), alpha-Smooth Muscle Actin, and nm23 Proteins in IB-IIB Uterine Cervical Cancer.: Hee Kyung Chang, Man Ha Huh, Dong Hee Kim, Un Dong Park; Korean J Pathol. 1997;31(6):546-556.

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Abstract PDF: We examined the expressions of CD44 splice variants (v4/5, v6), alpha-smooth muscle actin, nm23 to evaluate their roles as prognostic factors in 70 cases of uterine cervical carcinoma (stage IB to IIB) who were surgically treated from January 1989 to June 1990 with a clinical follow-up of a minimum of 5 years. The expression was examined by an immunohistochemical method using archival formalin fixed paraffin embedded tissue. In the 70 cases, 61 cases were squamous cell carcinoma and 9 cases were adenocarcinoma. CD44v4/5, CD44v6, alpha-smooth muscle actin, and nm23 were detected in 41.4%, 70%, 100%, and 74.3% of tumor samples, respectively. CD44 splice variants and nm23 showed membrane and cytoplasmic staining of tumor cells, respectively. The expression of alpha-smooth muscle actin showed cytoplasmic staining confined to stromal cells and was classified into three grades by the extent in stromal cells: with less than 10% of stromal cells; 32.9%, 10-50% of stromal cells; 40.0%, more than 50%; 27.1%. These expressions were not correlated with histologic types, lymph node involvement, recurrence, and grades of tumor infiltrating lymphocyte (TIL). But CD44v4/5 had significantly inverse correlation with TIL (p=0.049). The expression of CD44v4/5 was significantly correlated with that of CD44v6 (p=0.05), and that of alpha-smooth muscle actin was inversely correlated with that of nm23 (p=0.049). In conclusion, in FIGO IB-IIB uterine cervical carcinoma CD44 variants, nm23, and SMA show high prevalence, however, with little prognostic significance assessed by recurrence and lymph node metastasis.

E-Cadherin Expression and DNA Ploidy Analysis in Invasive Squamous Cell Carcinoma of the Uterine Cervix Comparison with those of CIN.: Yoo Jin Kim, Mee Young Sol, Man Ha Huh, Sun Kyung Lee; Korean J Pathol. 1997;31(6):557-565.

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Abstract PDF: Epithelial cadherin (E-cadherin) is a Ca2+ -dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss is associated with an invasive and poorly differentiated phenotype in a wide range of tumors. Formalin-fixed, paraffin-embedded tissue sections from 36 cases of cervical intraepithelial neoplasia (CIN) and 14 cervical squamous cell carcinomas were investigated for the expression of E-cadherin immunohistochemically. While E-cadherin expression was usually restricted on the cell membrane of basal and parabasal cells in normal cervix, the presence of cytoplasmic E-cadherin was found to be associated with its grade in CIN lesions. Also, marked cytoplasmic staining was commonly revealed in poorly differentiated ones than well-differentiated squamous cell carcinomas. More intense reactivity of cytoplasmic E-cadherin was frequently seen in the foci of invasion than adjacent carcinoma in situ, and in its periphery than the center of tumor islands. In addition, DNA ploidy and S-phase fraction of squamous cell carcinomas were analyzed and compared with those of CIN lesion. We found that invasive squamous cell carcinomas more frequently disclosed DNA aneuploidy than CIN lesions, and there was correlation between cytoplasmic E-cadherin expression and DNA aneuploidy. Also, cytoplasmic E-cadherin-reactive cervical neoplasms had a higher rate of cell proliferation than that of membranous E-cadherin-reactive cases. These data suggest that the increased cytoplasmic E-cadherin expression may represent one of the abnormalities underlying the loss of polarity and invasiveness of cancer cells, and the abnormal E-cadherin expression combined with/without DNA ploidy or S-phase fraction may serve as a prognostic indicator.

Clinicopathological Analysis on the 104 Cases of Malignant Melanoma.: Kye Yong Song, Kyeong Cheon Jung, Kwang Hyun Cho, Je Geun Chi, Eui Geun Ham; Korean J Pathol. 1997;31(6):566-573.

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Abstract PDF: The cliniopathological analysis was done on the 104 cases of malignant melanoma diagnosed at the Seoul National University Hospital (SNUH) from 1984 to 1993. The basic clinical data and the pathological items were based on the New Mexico Melanoma Registry Worksheet. The results were as follows. The male to female ratio was 1 : 0.79. Primary cutaneous melanoma was more common in the male (M : F=1 : 0.56) but primary extracutaneous melanoma with slight female dominancy (M : F=1 : 1.25). The peak age was the 6th decade in both cutaneous and extracutaneous malignant melanoma. In 66% (35 cases) of primary cutaneous malignant melanoma, the primary site was located in the acral area (including cases of acral lentiginous and nodular type), of which 63% (41% of total cutaneous melanoma) was acral lentiginous type. Major components of tumor cells were epithelioid. Clark's level of tumor was III or more at the time of the first visit in the majority of the cases (85%). The incidence rate of extracutaneous melanoma was 34.6% (36 cases) among the primary melanoma, and the eyeball (17.3%) was the most prevalent organ. All these features suggest that the racial difference between the Korean and the Caucasian is evident and also that etiologic role of sun damage is not quite marked in the Korean. We also suggest that an early detection program is very important to cure this malignant tumor.

Characterization of Principal Component Cell of DMBA induced Rat Malignant Fibrous Histiocytoma With Cell Culture and Cloning.: Myeng Sun Park, Hae Jin Jeong, Man Ha Huh; Korean J Pathol. 1997;31(6):574-585.

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Abstract PDF: This experiment was performed to elucidate the cytologic origin of chemically induced MFH in Wistar rats. The tumor was produced by injections of DMBA(9,10-dimethyl-1,2-benzanthracene). With the produced MFH, cell culture and cloning were performed, followed by establishment of a cell strain, which was investigated by immunohistochemical and electron microscopic studies. The results were as follows. A) By immunohistochemistry of the tumor tissue, fibroblastic cells were positive for MEP-1(specific antibody for fibroblastlike cell of MFH, Takeya, 1993) and Anti-hPH(beta)(Anti-prolyl 4-hydroxylase beta), but negative for TRPM-3 and F4/80. Histiocytelike cells were positive for TRPM-3 and F4/80, but negative for MEP-1 and Anti-hPH(beta). In immunoelectron microscopy, normal spleen macrophage showed linear reactivity in cell membrane for TRPM-3, whereas histiocytelike cells of the tumor disclosed negative reaction. B) At 5 weeks of the primary tumor cell culture, the cells exhibited typical storiform pattern of MFH. C) The established cell strain revealed immunoreactivity for MEP-1 and Anti-hPH(beta), but negative for TRPM-3. The cloned tumor cells showed morphologic characteristics of undifferentiated fibroblastic cell. Latex particle (0.80 micrometer size) phagocytosis was negative in the cloned cell strain. The results of the current study support the concept that principal component cells of MFH is of fibroblastic cell origin.

Case Reports

Infantile Hemangioendothelioma of the Liver: Brief case report.: Hyang Jeong Jo, Ki Jung Yun, Jae Kyu Lee, Ji Shin Lee, Hyung Bae Moon; Korean J Pathol. 1997;31(6):586-588.

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Abstract PDF: Infantile hemangioendothelioma of the liver is a common vascular tumor in infancy. The tumor is usually multinodular or diffuse and classified into two types. We present a case of infantile hemangioendothelioma of the liver, which predominantly consists of type 2. A 4-month-old female was admitted for an evaulation of an abdominal distension. A CT scan of the liver showed a multinodular mass. The right lobectomy was done. Grossly, the mass consisted of round nodules ranging from 2cm to 5cm in diameter. Microscopically, the tumor revealed proliferation of small vascular channels lined by endothelial cells. Bizarre cells and mitotic cells were frequently noted. Vesicular nuclei and multilayering of the endothelial cells were also noted.

Bilateral Elastofibroma: Report of a case.: Sung Chul Lim, Mi Sook Lee, You Kyung Jeong, Yun Shin Kim, Hyun Jong Park, Mi Ja Lee; Korean J Pathol. 1997;31(6):589-591.

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Abstract PDF: Elastofibroma is a rare benign tumor-like condition manifesting as firm and spherical mass with poorly circumscribed margins of fibroelastic tissue, occuring in the subscapular region or the chest wall of elderly persons. It is not a true neoplasm but rather a reactive or degenerative process causing abnormal elastogenesis. It is unilateral in the majority of cases and the right side is affected more commonly than the left. We report a case of bilateral elastofibromas removed from both subscapular regions of a 73-year-old female farmer. She was presented with tender masses on the bilateral subscapular areas for seven years. Microscopically, it consisted of a mixture of intertwining broad eosinophilic collagen bundles and elastic fibers associated with a few fibroblasts and mature fat cells. The elastic fibers had a degenerated beaded appearance or were fragmented into serrated globules in a linear arrangement.

Inflammatory Pseudotumor of the Kidney.: Hwa Eun Oh, Jeong Seok Moon, Sung Jin Cho, Nam Hee Won; Korean J Pathol. 1997;31(6):592-594.

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Abstract PDF: Inflammatory pseudotumor, originally described in the lung, is a relatively rare tumor-like lesion that occurs in various organs and tissues. It is usually well demarcated from the surrounding tissue, however it can be unfortunately resected as a malignant tumor. A few inflammtory pseudotumor in the kidney have been reported in English literature, but there have been no reports in Korea. We report a case with inflammatory pseudotumor of the kidney. A 48 year old woman had an intermittent flank pain on the right side. An ultrasonographic study suggested a renal cell carcinoma and a nephrectomy was done. Grossly, there were two separate masses with a well demarcated yellowish appearance, measuring 2.3 cm and 1.3 cm in diameter, respectively. Histologically, they were composed of smooth muscle actin positive spindle cells and a large number of foamy histiocytes, lymphocytes, and plasma cells in the fibrotic backgound.

Benign Cystic Mesothelioma.: Sung Chul Lim, You Kyung Jeong, Mi Sook Lee, Yun Shin Kim, Hyun Jong Park, Sang Joon Choi; Korean J Pathol. 1997;31(6):595-597.

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Abstract PDF: Benign cystic mesothelioma (BCM) is a rare mesothelial lesion that forms multicystic masses in the upper abdomen, pelvis and retroperitoneum. Although it is categorized as a benign lesion, it has a tendency to recur. It is uncertain whether the nature of this lesion is reactive or neoplastic, but many articles support the conclusion that it is reactive rather than neoplastic. The majority of cases were associated with a history of a previous abdominal or pelvic operation, or an evidence of endometriosis or a pelvic inflammatory disease, or a combination of these findings. In a 26-year-old woman we experienced a case of BCM which was incidentally discovered at cesarean delivery revealing multilocular thin and translucent walled cysts in the pelvic cavity. Microscopic examination revealed a thin cyst wall that was composed of fibrous connective tissue and lined by internal stratified and external nonstratified single cuboidal epithelia.

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