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Volume 31(7); July 1997
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Original Articles
Pathologic Analysis of Gallbladder Cancer by the Stage and Intestinal Metaplasia with the Diagnostic Significance of CEA and p53.
Hee Jin Chang, Jung Il Suh
Korean J Pathol. 1997;31(7):599-607.
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Twenty cases of gallbladder cancers were examined using 5 mm stepwise tissue sections. We analyzed the clinicopathologic findings of the early (stage 1, II) and advanced carcinoma (stage III, IV, V) and those of carcinoma with or without metaplasia in the tumor. We also performed CEA and p53 immunohistochemical staining and compared their findings with those of normal mucosa and preneoplastic lesions. The results were as follow: 1) All of the early carcinomas (n=5) were incidentally diagnosed after the resection for the gallstone. They were compared to advanced carcinoma (n=15) in the absence of the lymphatic or angioinvasion, recurrence, metastasis and death. 2) Metaplastic and non-metaplastic carcinoma did not reveal any difference of the clinicopathologic findings except age distribution. 3) CEA and p53 were positive in preneoplastic and malignant lesions. The extent of staining was related to the degree of the atypia. From the above results, an early detection of gallbladder cancer is very important for the prognosis of the patients. Since preoperative diagnosis is difficult, thorough pathologic examination of routinely resected gallbladder is necessary for the early diagnosis. CEA and p53 immunohistochemical staining may be helpful in the differential diagnosis of non-neoplastic and neoplastic lesion of the gallbladder.
Flow Cytometric DNA Analysis of Gastrointestinal Stromal Tumors .
Mee Yon Cho, Soon Won Hong, Soon Hee Jung, Hogeun Kim, Chanil Park
Korean J Pathol. 1997;31(7):608-616.
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To evaluate the correlation between the histologic grade and DNA ploidy or proliferation index/S phase fraction (SPF) of gastrointestinal stromal tumors, we performed the DNA analysis using the flow cytometry. Paraffin embedded tissue samples of 57 gastrointestinal stromal tumors were used. The sites of the tumors were: stomach (28), small intestine (23), and large intestine(6). DNA index, proliferative index, and SPF by the flow cytomery were compared with histologic grade. The histologic grade of the gastric tumors were benign (12), borderline (10), and malignant (6). Those of the small intestinal timors were benign (2), borderline (13), and malignant(8). The large intestine were borderline (2), and malignant (4). In stomach, aneuploidy was found in 25.0% of benign, 40.0% of borderline, and 100% of malignant. And there was statistically significant correlation between the histologic grade and ploidy (p < 0.05). By contrast, small and large intestinal tumors showed more frequent aneuploidy in benign than in malignant. The proliferative index was correlated with the histologic grade in gastric tumors (p<0.05), but the SPF was not. In conclusion, the ploidy and proliferative index of gastric tumors are closely correlated to the histologic grade. However, aneuploidy in tumors of the small and large intestine were difficult to predict the malignancy.
Microsatellite Instability and the Expression of Tumor-associated Genes in Multiple Cancer.
Kyung Soo Kim, Chan Choi, Chang Soo Park, Sang Woo Juhng
Korean J Pathol. 1997;31(7):617-627.
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Genetic changes associated with oncogenes or tumor suppressor genes are frequently observed in human cancers. These changes may be more frequent in multiple primary cancers than sporadic cancers. These experiments were designed in order to know the genetic changes using microsatellite PCR technique and the expression of tumor-associated genes by immunohistochemistry for c-myc and p53 in 17 cases of multiple primary carcinomas. The niicrosatellite instability (MSI) were found in 8 of 17 cases (47.1 %); six cases showed MSI in more than two microsatellite loci and two cases revealed MSI in one locus. MSI was found in 2 out of 7.patients (28.6%) of multiple primary carcinomas arising from the unrelated organs, and 6 out of 10 patients (60.0%) arising from the same or related organs. When each case of multiple primary carcinomas was examined, immunohistochemistry for c-myc was positive in 25 cases (71.4%) and p53 was positive in 21 cases (60.0%) out of 35 cases. But there was no correlation between MSI and expression of tumor-associated genes. From the above the results, MSI is more important in carcinogenesis of multiple primary carcinomas arising from the same or related organs than those from unrelated organs.
Computerization of Microscope Slide Labelling.
Dong Sug Kim, Dae Hong Suh
Korean J Pathol. 1997;31(7):628-634.
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The automation in surgical pathology, particularly in the reporting and encoding system using personal computers has been greatly improved in recent years, but the computerization of microscope slide labelling has not been improved. The authors have developed database program for slide labelling using FoxPro 2.5 and FoxBASE SCOUNIX 2.1.2: For I year during trial an effect has been put forward to simplify and organize the labelling work in routine surgical pathology. The program is now become easily applicable to the labelling work without disturbing the normal flow in a pathology laboratory. It is possible to get information concerning how many paraffin blocks and H&E slides have been made, as well as what kind of special stains have been requested for each case. The authors think that the computerization of labelling work in routine surgical pathology is a fairly easy task, and this should simplify the labelling work at a lower cost, diminish the workload of a typist or technician, and indirect information concerning the workload in a pathology laboratory can be calculated.
Prognostic Value of CD44v6 Isoform in Infiltrating Ductal Carcinoma of Breast.
Seung Cheol Lee, Yoon Kyung Sohn, Jung Sik Kwak, Woon Bok Jhung, Jung Wan Kim
Korean J Pathol. 1997;31(7):635-643.
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CD44 is a family of transmembrane glycoproteins involved in cell-cell and cell-matrix interactions. Expression of CD44 isofonns (splice variants) has been shown to be associated with poor prognosis in several human cancers. We evaluated the expression patterns of the CD44 isofortn (CD 44 splice variant v6) in infiltrating ductal carcinoma of the breast by immunohistochemical and RT-PCR method. Paraffin embedded blocks from seventy-five cases of mastectomized samples were analyzed immunohistochemically using monoclonoal antibody against CD44v6. CD44v6 was detected in fifty-seven cases (76%) of the tumor samples. Adjacent normal myoepithelial cells and ductal epithelial cells revealed focal positive reaction to CD44v6. Thirtytwo cases (80.0%) with lymph nodal metastasis revealed overexpression of CD44v6 monoclonal antibody, but twenty-five cases (71.4%) without nodal metastasis also showed positive reaction to CD44v6 monoclonal antibody, and there is no statistically significant value. Other prognostic factors of infiltrating ductal carcinoma, such as tumor size, histologic grade and hormonal receptors did not show any significant correlation with CD44v6 expression. The RT-PCR studies for 9 cases of infiltrating ductal carcinoma showed the same band patterns both in the normal and tumor tissues. From the above results, it is concluded that the expression of CD44v6 is not a valuable prognostic marker of infiltrating ductal carcinoma of breast.
Detection of the c-m c Oncogene Amplification in Ovarian Carcinomas by Differential Polymerase Chain Reaction.
Geun Shin Lyu, Chan Kum Park, Chun Geun Lee, Youl Hee Cho, Youn Yeoung Hwang, Jung Dal Lee
Korean J Pathol. 1997;31(7):644-654.
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The amplification of c-myc oncogene was evaluated in 42 cases of ovarian carcinomas to correlate with clinical parameters. Using oligonucleotide primers, sequences from the c-myc exon-3 gene and from a control gene, tissue plasminogen activator (tPA), were amplified simultaneously by polymerase chain reaction (PCR). After the products of differential PCR (d-PCR) were electrophoresed, slot blot hybridization was performed, and hybridized with P32 dATP-labeled myc and tPA oligonucleotide probes and then autoradiographed. The signal intensities of the two products were quantitated by densitometry and the ratios of two products (c-myc/tPA) were measured. The ovarian carcinomas showed significantly increased amplification of c-myc oncogene Oligonucleoti compared to normal control group (p<0.05). 15 of 42 cases (35.7%) showed various degrees of the MYC gene amplification up to 27 folds in various histologic types of ovarian carcinomas. No significant differences of the MYC gene amplification according to histologic subtypes, tumor action) grades and clinical stages of ovarian carcinomas were present.
Overexpression of p53 Protein in Endometrial Hyperplasia and Adenocarcinoma.
Yun Sin Kim, Mi Sook Lee, Sung Chul Lim, Jang Shin Sohn, Chae Hong Suh
Korean J Pathol. 1997;31(7):655-661.
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Proliferations of the endometrial glands form a continuum from focal glandular crowding through simple hyperplasia, complex hyperplasia and atypical hyperplasia to frank adenocarcinoma. But objective criteria to distinguish these proliferative endometrial lesions are not clear-cut and terminology is confusing. The p53 protein is a nuclear phosphoprotein that can regulate cell proliferation and suppress tumor growth. Mutation in the p53 gene have been reported in a variety of human tumors, and in selected malignancies overexpression of p53 has been associated with poor prognosis. In this study we examined a series of endometrial proliferative lesion, including hyperplasia, adenocarcinoma, and adenomyosis to determine whether or not p53 is overexpressed in these lesions. In the result, p53 immunoreactivity was observed in 3 of 17 (17.6%) simple hyperplasia, one of 6 (16.6%) complex hyperplasia, none of 3 (O%) atypical hyperplasia, 6 of 13 (46.1%) adenocarcinoma and none of 10 (O%) adenomyosis. In conclusion, p53 mutation seems to play a role in oncogenesis of endometrial adenocarcinoma in early phase but there was no significant relationship between p53 overexpression and histologic grade of adenocarcinoma.
Alteration of p53 Tumor Suppressor Gene in Hyperplastic Lesions and Adenocarcinomas of Uterine Endometrium - Immunohistochemistry and PCR-SSCP.
Eun Kyung Kim, Chan Kum Park, Gu Kong, Moon Hyang Park, Jung Dal Lee
Korean J Pathol. 1997;31(7):662-671.
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To investigate the role of the p53 gene in the development of endometrial adenocarcinoma and to study the relation between alteration of the p53 gene and histologic grade, the author studied the alteration of thep53 gene in hyperplastic lesions and adenocarcinomas of the uterine endometrium. The study was carried out with immunohistochemical stain and PCR-SSCP. The materials included ten cases of endometrial hyperplasia (five simple and five atypical complex) and 18 cases of endometrial adenocarcinoma. Overexpression of the p53 protein were found in one of five atypical complex hyperplasias (20%) and 11 of 18 adenocarcinomas (61.1%). The intensity of p53 overexpression appeared to have increasing tendency with higher histologic grade of adenocarcinomas. Among the II cases of adenocarcinoma that overexpressed p53 protien, five cases (45.5%) were found to have mutations by PCR-SSCP. One was grade 1 (20%), two were grade 11 (25%), and two were grade III (40%). The sites of mutation were three exon 8, one exon 5, and one exon 6. In conclusion, alteration of the p53 gene may paly a role in the development of endometrial adenocarcinoma and appears to occur as a late event in carcinogenesis.HHowever, inactivation of the p53 gene in early stage of tumor development cannot be excluded.
A Study on the Expression of p53 Oncogene Products, PCNA Index and DNA Ploidy in Renal Cell Carcinoma.
Jong Jae Jung, Ji Shin Lee, Chan Choi
Korean J Pathol. 1997;31(7):672-682.
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Mutant p53 is associated with the advanced stages of some human tumor but there is a wide variation in the reported incidence of p53 mutation in renal cell carcinoma and its prognostic significances. We designed this study to assess the expression of p53 in renal cell carcinomas and to compare with the established prognostic factors. Immunoreactivity for p53 protein and proliferating cell nuclear antigen (PCNA) were assessed in 44 cases of primary renal cell carcinoma, and flow cytometric analysis of DNA ploidy was perfon-ned in 37 of those cases. p53 protein was over-expressed in 16/44 (36.4%) renal cell carcinomas and 5 rumors had more than 10 immunoreactive tumor cells. The expression of p53 protein was positively related to nuclear grade (p=0.007) and PCNA index (p=0.002), but was independent of stage and DNA ploidy. In univariate survival analysis, stage (p<0.001), nuclear grade (p=0.017), DNA ploidy (p=0.045) and PCNA index (p<0.001) were significantly associated with patient survival. However, considering the stage, all of the last three factors had no prognostic influence. Cases showing strong positivity of p53 expression had worse prognosis than those with no or weak p53 expression, especially in early lesions (stage I,II) (p<0.001).
Case Reports
Ovarian Sertoliform Endometrioid Carcinoma.
Han Seong Kim, Won Ae Lee, In Ae Park, Eui Keun Ham
Korean J Pathol. 1997;31(7):683-687.
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Sertolifonn endometrioid carcinoma (SEC) is a very rare malignant neoplasm arising from the surface epithelium of the ovary. We report one case of SEC occuring in the left ovary of a 73-year-old woman. The left ovary was totally replaced by a yellowish tan lobulated solid mass with focal cystic areas. Small tubules and elongated solid cord-like structures resembling a Sertoli-Leydig cell tumor or a Sertoli cell tumor were found microscopically. In some areas, confluent typical endometrioid carcinoma, adenofibromatous stroma, squamoid foci, and lutenizing stromal cell nests were noted. The tumor also demonstrated strong immunoreactivity with EMA (epithelial membrane antigen). Certain points of differentiation between SEC and SertoliLeydig or Sertoli cell tumors are discussed.
Cellular Schwannoma Arising in a Facial Nerve.
Mee Joo, Hye Sung Kim, Yun Kyung Kang, Hye Kyung Lee, Jae Young Park
Korean J Pathol. 1997;31(7):688-691.
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Cellular schwaninoma is a variant of schwannoma, which is characterized by predominance of cellular Antoni A area, presence of mitotic activity, nuclear hyperchromasia, pleomorphism, and absence of Verocay body. These pathologic features often prompted a misdiagnosis of malignancy. However, the clinical outcome has indicated the benignity of the tumor. We have experienced a case of cellular schwannoma arising from right facial nerve with right hemifacial weakness and erosion of mastoid process. Grossly, it was a 3.5 x 3 cm sized and relatively well encapsulated mass with yellowish, friable cut surface. Microscopically, cellular growth with moderate cellular pleomorphism and some mitotic activity (5/40 HPFS, up to 2/HPF) were noted. Immunostaining for S-100 protein showed diffuse strong positive reaction.
Cystic Struma Ovarii Mimicking Adenomatous Goiter of the Thyroid.
Kee Taek Jang, Je Geun Chi
Korean J Pathol. 1997;31(7):692-694.
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Struma ovarii, the most common monodennal teratoma of the ovary, causes diverse problems in differential diagnosis. The literature on the pathology of struma ovarii has focused principally on the problem of formulating criteria of malignancy. In contrast, unusual gross and microscopic features of struma ovarii and its resultant problems in differential diagnosis have received relatively little attention. We report an ovarian teratoma which was almost entirely cystic, causing the diagnosis of struma to be overlooked. The removed ovarian tumor showed all the features of adenomatous goiter of the thyroid gland. The lining epithelium of the cysts was frequently flattened, and the follicles in the cyst wall were few and atrophic. The patient was a 58-year-old woman who was found to have an ovarian tumor by routine monographic examination

J Pathol Transl Med : Journal of Pathology and Translational Medicine