Journal of Pathology and Translational Medicine

Case Report

In Situ Follicular Lymphoma Developed after Hodgkin Lymphoma.: Ho Sung Park, Sang Jae Noh, Jae Yong Kwak, Eun Kee Song, Myung Hee Sohn, Ho Lee, Woo Sung Moon, Kyu Yun Jang; Korean J Pathol. 2011;45:S53-S57.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S53

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Abstract PDF: In situ follicular lymphoma is a newly defined entity among the lymphoid neoplasms and is defined as architecturally normal-appearing lymph nodes and other lymphoid tissues that have one or more follicles that demonstrate bcl-2 overexpressing centrocytes and centroblasts, with or without a monomorphic cytologic appearance suggestive of follicular lymphoma. Here we present a case of in situ follicular lymphoma diagnosed during the follow-up after a complete response to the treatment of lymphocyte-rich classical Hodgkin's lymphoma. In our case, because only a few germinal centers contained bcl-2 overexpressing cells, we missed the diagnosis of in situ follicular lymphoma in the initial histological examination. We could establish the diagnosis only after performing bcl-2 immunostaining in the sequential biopsy. Therefore, we recommend that careful histological examination along with bcl-2 immunostaining is needed in patients with suspicious clinical findings.

Original Articles

Immunohistochemical Study on the Expression of Mutated p53 Protein and Bcl-2 Protein in Melanocytic Lesions of Skin.: Wha Jin Lee, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1997;31(2):112-120.

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Abstract PDF: To investigate the immunohistochemical expression of mutated p53 protein and bcl-2 protein in the cutaneous melanocytic lesion, 15 cases of compound nevus, 10 cases of congenital melanocytic nevus, 15 cases of primary malignant melanoma(4 cases less than 1.5 mm thick and 11 cases more than 1.5 mm thick), and 10 cases of metastatic malignant melanoma(7 cases in lymph node and 3 cases in soft tissue) were examined. All cases of compound nevi and of congenital melanocytic nevi showed no immunoreactivity for p53 protein. p53 protein overexpression was observed in 75%(3/4) wth primary malignant melanoma less than 1.5 mm thick, 81%(9/11) with primary malignant melanoma more than 1.5 mm thick, and 100%(10/10) with metastatic malignant melanoma. The difference in p53 protein overexpression was statistically significant between benign nevi and malignant melanoma(p<0.01). Bcl-2 protein expression was observed in 73%(11/15) with compound nevus, 70%(7/10) with congenital melanocytic nevus, 75% (3/4) in primary malignant melanoma less than 1.5 mm thick, 54%(6/11) with primary malignant melanoma more than 1.5 mm thick, and 40%(4/10) with metastatic malignant melanoma. These findings suggested that mutation of p53 gene may be an important mechanism in the development of malignant melanoma. Although bcl-2 protein was expressed in cutaneous melanocytic lesion, no correlation was found between p53 protein and bcl-2 protein expression in malignant melanoma.

Histopathologic Re-evaluation of Thymoma with Immunonhistochemical Study for bcl-2 and MIC-2 Protein.: Kyung Moo Yang, Mee Yon Cho, Soon Won Hong, Tae Seung Kim, Chan Il Park, Woo Ick Yang; Korean J Pathol. 1997;31(5):446-461.

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Abstract PDF: We reviewed 86 thymic epithelial tumors and reclassified them according to the Kirchner and Muller- Hermelink classification. They were subtyped as medullary, mixed, predominantly cortical (organoid), cortical, well differentiated thymic carcinoma, and poorly differentiated thymic carcinoma. The frequency of each subtype was determined and histologic findings were related to stage and myasthenia gravis. Immunohistochemical stains for bcl-2 protein as a marker for medullary thymocytes and MIC-2 protein as a marker for cortical thymocytes were performed in each case. The stages and association of myasthenia gravis was significantly different in each subtypes. The results of this study demonstrate that this histogenetic classification is clinically applicable. The bcl-2 protein was specifically demonstrated in lymphocytes within areas of medullary differentiation and MIC-2 protein in cortical differentiation. The expression of bcl-2 and MIC-2 proteins lend histogenetic support for this new classification of thymoma. Bcl-2 protein is strongly expressed in tumor epithelial cells of every case of poorly differentiated thymic carcinoma whereas the other types of thymic epithelial tumors do not show epithelial expression of this protein. The strong expression of bcl-2 protein in tumor epithelium may be considered as a predictor of aggressive behavior in thymic epithelial tumors.

Expression of Epstein-Barr Virus Gene Products, Bcl-2 and p53 Proteins in Nasopharyngeal Carcinomas.: Sun Hee Yoon, Kang Suek Suh, Chang Hun Lee; Korean J Pathol. 1997;31(8):723-734.

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Abstract PDF: The authors studied EBV genome expression in 40 conventionally processed samples of nasopharyngeal carcinomas (NPC), using in situ hybridization for EBERs and immunohistochemistry for LMP, Bcl-2 and p53 proteins. The NPCs consisted of 6 keratinizing squamous cell carcinomas (KSCs), 13 nonkeratinizing carcinomas (NKCs) and 21 undifferentiated carcinomas (UCs). The results were summarized as follows: 1) EBERs were expressed in 80.0% of all the NPCs (32/40). As for the subtypes, they were detected in 92.3% of NKCs (12/13), in 90.5% of the UCs (19/21), and in 16.7% of the KSCs (1/6). In positive cases, the nuclei of tumor cells displayed uniformly strong staining. 2) LMP was expressed in 10.0% of all the NPCs (4/40), all of which were UC. The LMP expression in the UCs was not correlated to the expression of EBERs, Bcl-2 and p53 proteins. 3) Bcl-2 protein was detected in 85.0% of all the NPCs (34/40). As for the subtypes, they were detected in 92.3% of the NKCs (12/13), in 90.5% of the UCs (19/21), and in 50.0% of the KSCs (3/6). 4) p53 protein was detected in 75.0% of all the NPCs (30/40). As for the subtypes, they were detected in 81.0% of the UCs (17/21), in 69.2% of the NKCs (9/13), and in 66.7% of the KSCs (4/6). 5) In the NPCs the expression of EBER showed a significantly positive correlation with that of p53 or Bcl-2 protein. The above results indicate that the association of EBV with NPC is chiefly with poorly differentiated and undifferentiated carcinomas. Additionally, carcinomas commonly display widespread, strong immunoreactivity of Bcl-2 and p53 proteins over tumor cells. In conclusion, these observations indicate that the EBV-association in NPC appears to contribute to the overexpression of tumor-related genes during carcinogenesis.

Histopathologic Findings & Expression of bcl-2 of the Endometrium Analysis of 1,000 consecutive biopsies of uterine bleeding .: Hye Kyung Lee, Dong Geun Lee, Ho Lee, Sang In Shim; Korean J Pathol. 1998;32(3):208-214.

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Abstract PDF: We evaluated 1,000 consecutive endometrial curettage samples obtained over a 30 month period. The clinico-pathologic correlation was analysed according to Hendrickson's five criteria based on the practical view. The causes of uterine bleeding in decreasing order of occurrence were as follows: 1) hormonal imbalance lesions (49.2%) encompassing glandular and stromal breakdown suggesting anovulatory bleeding, proliferative phase endometrium, and disordered proliferative endometrium, 2) pregnancy associated lesions (24.2%), 3) organic lesions (13.5%), 4) endometrial hyperplasia (6.9%), and 5) inadequate specimen (6.2%). According to age, pregnancy related lesions were most frequent in the third decade. In the fourth, fifth, and sixth decades, hormonal imbalance lesions were the most common cause. In approximately 30% of the samples, there were two or three morphologic patterns such as anovulatory bleeding with an endometrial polyp, postabortal bleeding with inflammation, and glandular-stromal dissociation with a polyp, which suggested there was a variable histologic morphology in the same disease spectrum. Using immunohistochemical techniques we studied the hormonal dependency of bcl-2 oncoprotein in anovulatory bleeding, endometrial hyperplasia, and proliferative endometrium. 70% of anovulatory bleeding specimens showed weak positivity in the epithelial cytoplasm, and all cases of endometrial hyperplasia and carcinoma showed a strong positivity. These results suggest that there is a estrogenic hormonal dependency of apoptosis in the endometrium.

Expression of bcl-2 Protein in Gastric Adenoma and Adenocarcinoma.: Young Sill Kim, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1998;32(4):248-254.

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Abstract PDF: The bcl-2 oncoprotein confers a survival advantage to cells by blocking programmed cell death. Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. However, there have been only a few reports on expression of bcl-2 in human gastric adenocarcinoma. The aim of this study was to investigate the relationship between the expression of bcl-2 protein and several clinical and pathological parameters such as age, tumor site, size, histological type, depth of invasion, Lauren's classification, and grade. Immunohistochemical staining using monoclonal bcl-2 protein antibody, clone 124, was performed on paraffin embedded specimens from 23 gastric adenomas and from 45 gastric adenocarcinomas. The results are as follows. 1. Variable intensity of epithelial staining was noted from case to case, although the lymphocytic component showed similar intensity in all examples. The staining was located at the gland and mucous neck region of non-neoplastic epithelium. 2. The more differentiated type of gastric adenocarcinoma showed the higher expression rate and intensity. 3. The relationship between the expression rates of bcl-2 protein and tumor grade (adenoma early gastric adenocarcinoma advanced gastric adenocarcinoma) was statistically significant. The reactivity in adenoma was somewhat stronger with a uniform pattern, while in adenocarcinoma it was much weaker with a heterogenous pattern. 4. Intestinal type carcinomas by Lauren's criteria showed a higher expression rate and intensity than diffuse type. These results suggest that the bcl-2 expression would be found in the early phase of gastric tumorigenesis, and the expression rate and intensity would decrease according to the tumor progression.

Correlation between Expression of p53 and Bcl-2 Protein and Epstein-Barr Virus Detection in Gastric Adenocarcinoma.: Ki Jung Yun, Weon Cheol Han, Hyung Bae Moon, Sang Woo Juhng; Korean J Pathol. 1998;32(8):574-580.

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Abstract: Epstein-Barr virus (EBV) has been known to be associated with a wide variety of neoplastic conditions including nasopharyngeal carcinoma, Hodgkin's disease, and non-Hodgkin's lymphoma. Recent studies reveal the presence of EBV in certain subtypes of gastric carcinoma in which EBV appears to be pathogenetically related. To evaluate the relationship between EBV and gastric adenocarcinoma, we examined EBV DNA using direct in situ polymerase chain reaction, and expression of p53 protein and bcl-2 protein using immunohistochemical staining method on paraffin embedded tissues. The materials consisted of one hundred twenty-eight gastric adenocarcinomas and twenty benign peptic ulcers. EBV DNA was detected in 14 of 128 gastric adenocarcinomas (10.9%). p53 protein was positive in 10 of 14 EBV positive adenocarcinomas (71.4%) and in 61 of 114 EBV negative adenocarcinomas (53.5%). Bcl-2 protein was positive in 2 of 14 EBV positive adenocarcinomas (14.3%) and in 19 of 114 EBV negative adenocarcinomas (16.7%). The above results indicate that EBV is associated with gastric adenocarcinoma, and p53 protein may play a role in carcinogenesis of EBV in gastric adenocarcinoma.

An Analysis of p53, bcl-2 and Ki-67 Expressions, and Apoptosis in Rectal Cancer: Their Correlation with the Tumor Response after Preoperative Radiochemotherapy.: Jinyoung Yoo, Su Zy Kim, Hyeon Min Cho, Sung Whan Kim, Hyung Min Chin, Jung Yong Lee, Jun Ki Kim, Seok Jin Kang, Chung Soo Chun, Chang Suk Kang; Korean J Pathol. 2005;39(4):222-228.

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Abstract PDF: Background
: Preoperative radiochemotherapy (RCT) has been administered for locally advanced rectal cancer to increase the therapeutic benefits, and to preserve the sphincter in low-lying tumors, however, tumor responses after RCT are variable. Methods : Apoptotic index (AI), and expressions of Ki-67, p53 and bcl-2 were analyzed in pretreatment biopsies from 69 patients with rectal cancer by immunohistochemistry. Tumor response was graded in surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR). Results : CR was identified in 19 cases (28%), PR in 24 cases (35%), and NR in 26 cases (38%) of 69 cases. p53 protein was expressed in 49 cases (71%), whereas bcl-2 was in 42 cases (61%). The pretreatment Ki-67 labeling index was 65.4+/-3.4%. The tumor response was not associated with any of these markers. Tumors with CR/PR showed a higher AI (0.84+/-.84%/0.66+/-.52%) than that of tumors with NR (0.58+/-0.54%). There was a significant correlation between tumor response and the histologic differentiation (p=0.008) or recurrence (p=0.039). Conclusions : The AI revealed a tendency to increase in tumors with CR/PR, while expressions of p53 and bcl-2, and Ki-67 labeling index had little direct association with tumor response.

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