Journal of Pathology and Translational Medicine

Original Articles

The proteomic landscape shows oncologic relevance in cystitis glandularis: Jun Yong Kim, Dohyun Han, Hyeyoon Kim, Minsun Jung, Han Suk Ryu; J Pathol Transl Med. 2023;57(1):67-74. Published online December 22, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.24

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Background
The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear.
Methods
We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation.
Results
We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG.
Conclusions
Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

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Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma
Jun Yong Kim, Jae Seok Lee, Dohyun Han, Ilias P. Nikas, Hyeyoon Kim, Minsun Jung, Han Suk Ryu
Heliyon.2024; 10(15): e35475. CrossRef
KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis
Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P. Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu
Pathobiology.2024; : 1. CrossRef

The Expression of Pigment Epithelium-Derived Factor in Bladder Transitional Cell Carcinoma: Tae Jung Jang, Sung Woo Kim, Kyung Seop Lee; Korean J Pathol. 2012;46(3):261-265. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.261

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Abstract PDF

Background

Pigment epithelium-derived factor (PEDF) is an anti-angiogenic factor. The purpose of this study is to examine the involvement of PEDF in the angiogenesis and biological behavior of bladder transitional cell carcinoma (TCC).

Methods

We examined the expression of PEDF in 99 bladder TCCs and ten non-neoplastic tissues, and evaluated microvessel density (MVD).

Results

The positive immunoreactivity for PEDF was seen in normal urothelium in 60% (6/10) and TCC in 13% (13/99). The PEDF expression had a significant correlation with MVD, i.e., a low MVD in 42% (5/12), a middle MVD in 11% (8/76) and a high MVD 0% (0/11) of tumors. The PEDF expression was not significantly correlated with the differentiation and invasion of TCC, but the degree of MVD was significantly higher in both high grade TCC and the pT2 tumors.

Conclusions

The degree of PEDF expression is significantly higher in normal bladder urothelium than bladder TCC; it is inversely correlated with the angiogenesis; and it is not related to the differentiation and progression of TCC. It can therefore be concluded that bladder TCC would initially occur if there is a lack of the PEDF expression.

Citations

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Association of pigment epithelium derived factor expression with cancer progression and prognosis: a meta-analysis study
Guo Cheng, Crystal Song
Discover Oncology.2021;[Epub] CrossRef
Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and pT1) at initial bladder biopsy is a simple and powerful predictor of clinical outcome: a multi-center study in South Korea
Ji Eun Kwon, Nam Hoon Cho, Yeong-Jin Choi, So Dug Lim, Yong Mee Cho, Sun Young Jun, Sanghui Park, Young A. Kim, Sung-Sun Kim, Mi Sun Choe, Jung-dong Lee, Dae Yong Kang, Jae Y. Ro, Hyun-Jung Kim
Diagnostic Pathology.2017;[Epub] CrossRef
Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer
Eun-Kyung Kim, Hye-Jung Kim, Young-Il Yang, Jong Tae Kim, Min-Young Choi, Chang Soo Choi, Kwang-Hee Kim, Jeong-Han Lee, Won-Hee Jang, Soon-Ho Cheong
Korean Journal of Pathology.2013; 47(6): 507. CrossRef

Expression of DNA Topoisomerase II-alpha as a Proliferating Marker in Urothelial Carcinoma of Urinary Bladder based on World Health Organization/International Society of Urological Pathology Consensus Classification: A Correlation with Expression of Ki-67 and Apoptosis: Tae Jin Lee, Dong Ki Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2002;36(5):305-313.

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Abstract PDF: BACKGROUND
DNA topoisomerase II-alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relationship between the expression of DNA topoisomerase II-alpha as a proliferating marker, and the expression of Ki-67 and apoptosis in urothelial carcinoma of urinary bladder based on World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification.
METHODS
73 urothelial carcinomas of the urinary bladder after transurethral resection and 25 carcinomas after radical cystectomy were investigated for histologic grading based on WHO and WHO/ISUP consensus classification. Formalin fixed, paraffin embedded tissue of 98 specimens from 73 patients were immunohistochemically stained for DNA topoisomerase II-alpha and Ki-67, and in situ TdT-mediated dUTP-biotin nick end labeling method for evaluation of apoptotic cells was performed. For each case, a DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were determined.
RESULTS
The histologic grades of 73 cases based on the WHO grading system were 21.9% (16 cases) in grade 1, 65.8% (48 cases) in grade 2, and 12.3% (9 cases). 5.5% (4 cases) of papillary neoplasm of low malignant potential, 47.9% (35 cases) of urothelial carcinoma of low grade, and 46.6% (34 cases) in urothelial carcinoma of high grade were reclassified using the WHO/ISUP consensus classification. Histologic grades based on two grading systems were correlated to invasion and stage (p<0.05). DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were correlated to histologic grades based on two grading system and invasion. Also, the correlation of DNA topoisomerase II-alpha and Ki-67 indices, and DNA topoisomerase II-alpha and apoptotic indices were significant, respectively.
CONCLUSIONS
DNA topoisomerase II-alpha appears to be an useful marker for assessing the proliferation potential of urothelial carcinoma of in the urinary bladder.

Cytologic Features of Prostatic Adenocarcinoma in Urine: Comparison with Urothelial Carcinoma.: Lucia Kim, Joo Young Song, Suk Jin Choi, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu; Korean J Pathol. 2011;45(1):79-86.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.79

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Abstract PDF

BACKGROUND
Prostate adenocarcinoma (PACa) cells are rarely identified in urine cytology specimens and might be easily overlooked or misdiagnosed as urothelial neoplasm when clinically unsuspected.
METHODS
We reviewed 19 urine cytology specimens obtained from 13 patients with PACa and evaluated the characteristic features discriminating PACa from urothelial carcinoma (UCa). For comparison, 27 cases of high-grade UCa (HGUCa) and 10 cases of urothelial carcinoma in situ (UCis) were also evaluated.
RESULTS
The urine cytologic evaluation of PACa revealed clustered cells forming 3-dimensional syncytial fragments with occasional microacinar grouping in a clean background. Most tumor cells were small and uniform with a high nuclear-to-cytoplasmic ratio and indistinct cell borders. The nuclei were round-to-oval and the cytoplasm was scanty and thin. One or more centrally-located prominent nucleoli were characteristically noted in one half of the cases. The nucleoli had a well-defined, large, round and eosinophilic appearance. In four high-grade cases, large tumor cells were encountered and had relatively monotonous cells with smooth-outlined cell clusters, well-defined and thin cytoplasm, and round nuclei with characteristic prominent nucleoli.
CONCLUSIONS
Combining the information of prostate cancer and the recognition of cytomorphologic features of PACa will help differentiate PACa from HGUCa and UCis.

Citations

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The diagnostic challenge of suspicious or positive malignant urine cytology findings when cystoscopy findings are normal: an outpatient blue-light flexible cystoscopy may solve the problem
Marie Andersson, Marthe Berger, Karsten Zieger, Per-Uno Malmström, Mats Bläckberg
Scandinavian Journal of Urology.2021; 55(4): 263. CrossRef
Sensitive Time-Gated Immunoluminescence Detection of Prostate Cancer Cells Using a TEGylated Europium Ligand
Nima Sayyadi, Irene Justiniano, Russell E. Connally, Run Zhang, Bingyang Shi, Liisa Kautto, Arun V. Everest-Dass, Jingli Yuan, Bradley J. Walsh, Dayong Jin, Robert D. Willows, James A. Piper, Nicolle H. Packer
Analytical Chemistry.2016; 88(19): 9564. CrossRef

Case Report

Urothelial (Transitional Cell) Carcinoma Arising in Mature Cystic Teratoma: A Case Report.: Ok Jun Lee, Ho chang Lee; Korean J Pathol. 2010;44(6):666-669.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.666

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Abstract PDF

Mature cystic teratoma (MCT) is one of the most common benign ovarian tumors, but 1-2% of MCTs are transformed to a malignant neoplasm. Urothelial carcinoma (UC) or transitional cell carcinoma is the most common cancer in the urinary tract. However, UC is a very rare component of transformed malignancy of MCT. Here we report a case of UC arising in an MCT in a 52-year-old woman. Grossly, the ovary was partly cystic and partly solid. Microscopically, the cyst revealed the classic features of MCT and the solid area was papillary UC. By immunohistochemistry using cytokeratins and thrombomodulin, the UC showed a similar expression to that of UC arising in the urinary tract, rather than resembling a primary transitional cell carcinoma of the ovary. When UC is found in a component of MCT, the origin of the carcinoma should be evaluated and urinary tract examinations are required to rule out metastasis.

Citations

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A Rare Urothelial Malignant Transformation in a Mature Cystic Teratoma of the Ovary
Moito Iijima, Iori Kisu, Tetsuro Shiraishi, Rie Irie, Nobumaru Hirao
Cureus.2021;[Epub] CrossRef
Transitional Cell Carcinoma arising in Ovarian Cystic Teratoma: A Rare Case Report
Abhay V. Deshmukh, Vitaladevuni B. Shivkumar, Neha V. Fulzele, Nitin M. Gangane
Indian Journal of Gynecologic Oncology.2020;[Epub] CrossRef
A Rare Malignant Transformation of an Ovarian Cystic Teratoma: A Case Report
Manju Rachel Mathew, Anita Ramdas, Susy S. Kurian, Linu Kuruvilla, Neelima Singh
Case Reports in Pathology.2018; 2018: 1. CrossRef
Urothelial carcinoma arising from an ovarian mature cystic teratoma
Hui-Yu Chuang, Yi-Ting Chen, Tak-Loi Mac, Yu-Chieh Chen, Hung-Sheng Chen, Wan-Shan Wang, Eing-Mei Tsai
Taiwanese Journal of Obstetrics and Gynecology.2015; 54(4): 442. CrossRef

Original Articles

Immunohistochemical Study for p53 and hsc70 in Transitional Cell Carcinoma of the Urinary Bladder: Correlation with Histologic Grade, Clinical Stage and DNA Ploidy Pattern.: Hyuni Cho, Sung Jin Cho, Han Kyeom Kim, Yang Seok Chae; Korean J Pathol. 1995;29(6):766-775.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the genitourinary tract in Korea and its prognosis is determined by the histologic grade and clinical stage present at initial diagnosis. Recently, an extensive search for a more objective and reproducible method to evaluate the proliferation activity of cancer cells has been done. The p53 gene is located on the short arm of the chromosome 17 and acts as a cancer suppressor gene. Mutant p53 gene induces malignant transformation. Recent studies reveal that the level of mutant p53 protein is elevated in some human tumor and many diverse transformed cell lines. Heat shock proteins(HSPs) are present constitutively in normal cells, where they play an important role in normal cell metabolism. In mammalian cells, they are induced by a variety of physical and chemical stimuli. A protein that belongs to the hsp70 family, called hsc70, is only slightly heat inducible and is found at a higher level in growing cells than in the resting cells. The mutant p53 protein binds with hsc70 and the p53-hsc70 complex has functional significance in the transforming capacity of the mutant p53. We investigated the correlation between the p53 and hsc70 by immunohistochemical methods and with better defined prognostic indicators such as histologic grade, clinical stage, and DNA ploidy pattern in 42 transitional cell carcinomas of the urinary bladder. The results are summarized as follows. p53 expression rate was higher in the DNA aneuploid group than in the DNA diploid group(p=0.061), but there was no significant difference in the histologic grade(p=0.861) or clinical stage(p=0.154). The higher the hsc70 expression rate was, the poorer the tumor differentiation(p=0.000) and the deeper the invasion(p=0.001). The aneuploid group showed a higher hsc70 expression rate than the diploid group(p=0.017). 27 of 42(64.3%) carcinomas showed positivity of both p53 and hsc70. Though statistically insignificant, their correlation showed a relatively low correlation coefficient (P=0.059). In conclusion, we suspect that p53 and hsc70 are closely correlated to each other by comparing the results of this immunohistochemical study, and hsc70 will be a useful prognostic marker in transitional cell carcinomas of the urinary bladder after sufficient follow up studies are performed.

Correlation between Histopathologic Grade, Stage, and Degree of EGFR Expression in Transitional Cell Carcinoma of the Urinary Bladder.: Hyeon Ok Kim, Hwa Sun Lee, Kang Suek Suh; Korean J Pathol. 1996;30(9):784-791.

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Abstract PDF: This study was performed to estimate the correlation between the histopathological grade and the clinical stage, which are known as important prognostic factors, and EGFR expression status in 57 cases of transitional cell carcinoma of the urinary bladder. There was a significant correlation between the histopathological grade and clinical stage of transitional cell carcinoma of the urinary bladder and between expression grades of EGFR and histopathological grades, or clinical stages of transitional cell carcinoma of the urinary bladder. Therefore, the presence of a high intensity of EGFR staining in the transitional cell carcinoma of the urinary bladder was associated with poor differentiation and invasion. On the basis of the above results, it was suggested that the degree of EGFR expression is one of the objective and reliable prognostic factors in transitional cell carcinoma of the urinary bladder.

Expressions of Epidermal Growth Factor Receptor, c-erbB-2 and p53 Protein as Useful Markers of Malignant Potential in a Transitional Cell Carcinoma of the Urinary Bladder.: Gu Kong, Ki Yong Shin, Sun Jin Kim, Young Hyeh Ko, Hae Young Park, Young Nam Woo, Jung Dal Lee; Korean J Pathol. 1997;31(1):51-58.

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Abstract PDF: Transitional cell carcinoma(TCC) of the urinary bladder shows marked heterogeneity in biological behaviors. Evidence has accumulated that biological markers may provide significant information to predict the potential aggressiveness of TCC. We have assessed the expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 and p53 proteins in 56 cases of TCC to investigate the prognostic significance of differential expression of these oncoproteins using an immunohistochemical method. We analysed the expression patterns of these oncoproteins according to tumor stage and grade. And we assessed the probability of progression-free survival in stage T1 tumors according to their expressions. Positive rates of EGF-R (>+3 staining intensity), c-erbB-2 (intense membrane staining) and p53 proteins (>20% positive cells) were 73.2%, 37.5% and 42.9%, respectively. Invasive tumors had significantly higher positive rates of all three factors than did superficial tumors (p<0.005 for EGF-R and c-erbB-2, p<0.05 for p53). High grade tumors had significantly higher positive rates of c-erbB-2 and p53 proteins (p<0.005). In superficial tumors, T1 tumors had higher positive rate of p53 protein compared with Ta tumors (p<0.05). Twelve cases of superficial tumors (34.3%) were positive for EGF-R and negative for c-erbB-2 and p53 proteins. Nine cases of superficial tumors(25.7%) were negative for all three factors. In invasive tumors, however, 42.5% of the cases were positive for all three factors. The overexpression of p53 protein was the only useful marker to predict the rapid progression in stage T1 tumors (p<0.05, log-rank test). These results suggest that the differential overexpression of EGF-R, c-erbB-2 and p53 proteins could be useful to depict tumor aggressiveness of TCC of the urinary bladder. And, the overexpression of a p53 protein may be a useful marker to predict the possibility of rapid progression in stage T1 tumors.

Prognostic Significance of PCNA Index and AgNORs Score in Transitional Cell Carcinoma of the Renal Pelvis.: Wan Seop Kim, Seung Sam Paik, Nam Hoon Kim, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(7):521-530.

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Abstract: Proliferative activity of a malignant tumor is known to reflect its biological aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells. In transitional cell carcinoma of the renal pelvis, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNORs count in 22 transitional cell carcinoma of the renal pelvis to assess their prognostic significance compared with their cumulative survival rate, the stage of disease and histopathologic features of the tumors. An immunohistochemical method and a standard colloidal silver staining were used. The mean percentage of PCNA positivity (PCNA index) and the mean number of AgNORs per nucleus (AgNORs score) were determined. In a multivariable analysis, PCNA indexes were significantly associated with tumor stage (p=0.024), whereas AgNORs scores were not significantly associated with the stage or histopatholgic features of the tumors. Histologic grade was correlated to disease stage at a significant level (p=0.000). But there was a trend of low tumor PCNA-indices or AgNORs counts with survival advantage for patients, but this did not reach statistical significance. The results suggest that the fraction of PCNA positive nuclei would be useful for investigating the malignant potential of renal pelvic cancers, although their clinical use as markers of biologic behavior may be limited.

Case Report

Sarcomatoid Transitional Cell Carcinoma of the Renal Pelvis A report of two cases.: Kyo Young Lee, Mi seon Kwon, Yeong Jin Choi, Chang Suk Kang, Seok Jin Kang, Baying Kee Kim, Sang In Shim; Korean J Pathol. 1999;33(2):128-132.

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Abstract: Sarcomatoid carcinomas are malignant epithelial neoplasms in which the tumor cells assume a partial or complete spindle cell pattern of growth, leading to the erroneous classification of some true carcinomas as sarcomas. These spindle cells are malignant and manifest various amount of both vimentin and cytokeratin. Positive reaction of some of the spindle cells for cytokeratin antibodies is confirmatory. Clinical features do not differ significantly from those of patients with high-grade transitional cell carcinoma. So far, 13 cases of sarcomatoid transitional cell carcinoma of the renal pelvis have been reported in English and Korean literature. In this report, we describe clinicopathologic features of recently observed two cases of sarcomatoid transitional cell carcinoma of the renal pelvis and summarize the pathologic findings of previously reported cases with review of the literature.

Original Articles

Expression of p27Kip1 Protein in Carcinoma of the Urinary Bladder.: Ki Kwon Kim, Jung Ran Kim; Korean J Pathol. 2000;34(5):341-348.

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Abstract PDF: The cyclin-dependent kinase (cdk) inhibitor p27Kip1 gene is a powerful molecular determinant of cell cycle progression. Loss of expression of p27Kip1 has recently been shown to be predictive of disease progression in several human malignancies. The prognostic value and expression of p27Kip1 have been incompletely studied in bladder cancer. In this study, we investigated the relationship between p27Kip1 protein expression and clinicopathologic parameters in 50 cases of carcinoma of the urinary bladder by conducting immunohistochemical analysis and DNA flow-cytometry. Malignant bladder tissue demonstrated a heterogeneous pattern of p27Kip1 immunoreactivity. In addition, there was progressive loss of expression with increasing tumor grade. The expression of p27Kip1 protein was unrelated to stage, DNA ploidy and S phase fraction (SPF). SPF was unrelated with tumor grade and DNA ploidy. The results indicate that p27Kip1 is frequently expressed in well differentiated transitional cell carcinomas of the urinary bladder but less often expressed in muscle-invasive transitional cell carcinomas. The expression of p27Kip1 and its prevalence in low-grade tumors may reflect growth regulatory influences and potential inhibiting action in tumor progression and novel predictive markers of the biological potential of bladder tumors.

Expression of c-erbB-2, c-myc, c-fos, bcl-2, p53, PCNA, and TGF-alpha in Transitional Cell Carcinoma of the Urinary Bladder.: Keun Hong Kee, Yoon Kyeong Oh; Korean J Pathol. 2000;34(7):516-523.

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Abstract PDF: Most of malignant tumors in the urinary bladder is transitional cell carcinoma (TCC) deriving from the urothelium. Clinical stage and histopathologic grading of the TCC of the urinary bladder is important in the determination of the patient's prognosis. To investigate the correlation between the prognostic factors and the expression of the various oncoproteins and growth factors in each grade of the TCC, immunohistochemical stains for c-erbB2, c-myc, c-fos, bcl-2, p53, proliferating cell nuclear antigen (PCNA), and transforming growth factor-alpha (TGF-alpha) were performed in the formalin fixed paraffin embedded tissues of the TCC (Grade I; 15 cases, Grade II; 20 cases, Grade III; 15 cases) of the urinary bladder. The immunoexpression rate of c-erbB2 was immunoexpression 78.0% in the grade I, 85.0% in the grade II, and 95.0% in the grade III TCC. The immunoexpression rate of c-myc, c-fos and bcl-2 was below 5% in each grades of TCC. The p53 immunoexpression was identified in 11.5%, 24.3% and 30.6% of the grade I, II, and III TCC, respectively. The PCNA and TGF-alpha expression was 53.0% and 27.6% in the grade I, 77.3% and 32.7% in the grade II, and 78.2% and 37.3% in the grade III TCC, respectively. These results suggest that the expressions of c-myc, c-fos, bcl-2, and TGF-alpha are similar in each grade of the TCC and the positivity of c-erbB2, p53, and PCNA shows an increasing tendency for the higher grade TCC of the urinary bladder. Therefore, c-erbB2, p53, and PCNA are clinically useful predictors of the patient's prognosis.

Expression of bcl-2 and p53 Protein, and Apoptosis in Transitional Cell Carcinoma of the Bladder.: Myoung Ja Chung, Sang Su Kim, Ho Yeul Choi; Korean J Pathol. 2000;34(8):567-573.

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Abstract PDF: This study examined the expression of the bcl-2 protein in 59 cases of transitional cell carcinomas (TCCs) of the bladder and evaluated the relationship of bcl-2 and p53 with apoptosis. The cases were divided into 41 low-grade TCCs, 18 high-grade TCCs, 32 superficial TCCs, and 27 invasive TCCs. p53 and bcl-2 protein were detected by the immunohistochemical method and apoptosis was analysed by using hematoxylin-eosin stained slide. The results were as follows: bcl-2 protein was detected in 8 (14%) TCCs and all of these cases were low grade TCCs. Expression of bcl-2 protein was not correlated with clinical stage. There was no correlation between bcl-2 and p53 protein. According to the immunohistochemical results of bcl-2 and p53 protein, the cases were divided 4 groups. Apoptotic index (AI) was higher in p53 positive/ bcl-2 negative group than other groups but the significance was recognized only between p53 positive/bcl-2 negative group and p53 negative/bcl-2 negative group (p<0.05). p53 protein was detected in 20 (36%) TCCs and its expression was correlated positively with histologic grade and clinical stage (p<0.05). AI correlated positively with histologic grade and clinical stage (p<0.01). These data indicate that overexpression of bcl-2 protein is rare in TCC of the bladder and associated with low grade TCCs. Overexpression of p53 is associated with the tumor progression in the TCCs. AI correlates with p53 positivity but does not correlate with bcl-2 positivity.

Cyclin D1 Protein Expression is Inversely Correlated with p53 Protein in Primary and Recurrent Transitional Cell Carcinoma of the Urinary Bladder.: Min Jin Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(12):1009-1015.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the urinary tract and is characterized by frequent recurrence. Like the other malignant tumor, the genetic alterations leading to neoplastic transformation of the urothelium are related with the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 is a putative protooncogene as cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumor. In this study we performed immunohistochemical stainings of cyclin D1 and p53 in both primary and recurrent transitional cell carcinomas of urinary bladder from 56 patients including 20 cases of recurrent tumor, and compared their results with histopathologic features. The results were as follows. Cyclin D1 immunoreactivity was found in 10 of 10 cases (100%) of grade 1, 25 of 41 (61%) cases of grade 2, and 11 of 25 (44%) cases of grade 3 transitional cell carcinomas. p53 immunoreactivity was found in 40% of grade 1, 63% of grade 2, and 87% of grade 3 lesions. Cyclin D1 expression was significantly higher in Ta and T1 lesions than T2 to T4 by pathologic tumor stage. Conversely p53 immunoreactivity was increased in proportion to the T classification. Cyclin D1 was de creased in recurrent transitional cell carcinomas, compared with primary transitional cell carcinomas. However, there was no statistical significance. In conclusion, cyclin D1 immunoreactivity is associated with low histologic grade and low tumor stage. And there is inverse relationship between the cyclin D1 and p53 overexpression.

Case Report

Ipsilateral Synchronous Renal Cell Carcinoma and Transitional Cell Carcinoma: A Case Report.: Ji Young Park, Eun Kyung Kwak, Tae In Park; Korean J Pathol. 2002;36(6):429-432.

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Abstract PDF: We report a synchronous renal cell carcinoma (RCC) and renal pelvic transitional cell carcinoma (TCC) in the kidney of a 74-year-old man. The kidney was without hydronephrosis. The patient was admitted to the hospital because he had intermittent gross hematuria for three years. Histologically, a section of the specimen revealed a conventional (clear cell) RCC in renal parenchyma just beneath the renal pelvis and a papillary urothelial carcinoma arising from the renal pelvis at the upper pole; the two are completely separated from one another. The tumor cells of the TCC showed an overexpression of c-MET immunohistochemical staining and more intense positive reactivity for p53 immunohistochemical staining than those of the RCC. These findings suggest that c-Met and p53 may be associated with the development of papillary TCC.

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