Journal of Pathology and Translational Medicine

Original Articles

Functional Inactivation of pRb Associated with Cyclin D1- and Cyclin-dependent Kinase 4 Overexpression Plays A Key Role in Human Pituitary Tumorigenesis.: Na Hye Myong; Korean J Pathol. 2009;43(1):56-62.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.56

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BACKGROUND
Human pituitary adenoma (PA) is a common intracranial tumor, but the mechanism underlying tumorigenesis has not been established. Functional inactivation of retinoblastoma protein (pRb) following cyclin D1- and cyclin-dependent kinase (CDK) 4-dependent hyperphosphorylation is one of the most important mechanisms in tumor cell proliferation. We evaluated immunohistochemical expressions of cyclin D1, CDK4 and phosphorylated pRb (p-pRb) in 50 PAs to investigate a role for functional inactivation of pRb associated with cyclin D1/CDK4 overexpression in pituitary tumorigenesis and to correlate it with clinicopathologic variables.
METHODS
Fifty human PAs were immunohistochemically stained for cyclin D1, CDK4 and p-pRb (Thr 356). Correlations between their expression and the clinicopathologic characteristics were statistically analyzed.
RESULTS
Cyclin D1 and CDK4 were overexpressed in 56% and 64%, respectively; pRb was hyperphosphorylated in 64%. Forty one cases (82%) showed one or more of these altered expressions. Overexpressions of cyclin D1 and CDK4 were correlated with functional pRb inactivation. Cyclin D1 overexpression was associated with apoplexy and growth hormone production.
CONCLUSIONS
Functional inactivation of pRb associated with the cyclin D1/CDK4 overexpression might play a key role in human pituitary tumorigenesis. CDK4 worked in concert with cyclin D1 to hyperphosphorylate pRb. Pituitary apoplexy appeared to be associated with cyclin D1 overexpression.

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Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27/Kip1 labeling indices
Iman H. Hewedi, Wesam M. Osman, Manal M. El Mahdy
Journal of the Egyptian National Cancer Institute.2011; 23(4): 171. CrossRef

Expression of p16 and Rb in 9,10-Dimethyl-1,2-Benzanthracene Induced Rat Ovarian Carcinogenesis.: Ki Kwon Kim, Dong Hun Kim; Korean J Pathol. 2001;35(2):144-150.

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Abstract PDF: BACKGROUND
In order to investigate the roles of p16 and Rb, their expression was evaluated in 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced ovarian cancers of rats.
METHODS
DMBA-coated silk was inserted into both ovaries of 20 9-week-old Sprague-Dawley rats. The experimental period lasted 20 weeks. The tumor histology was classified and the expression of p16 and Rb in the ovarian tumors was analyzed by immunohistochemistry and Western blot.
RESULTS
The p16 and Rb labeling index was significantly lower in the ovarian cancers than the normal ovarian surface epithelium of a rat. There were no differences among the cancer types. In Western blot analysis, the expressions of p16 and Rb in ovarian cancers were lower than those in normal ovarian tissue. No correlation was present between p16 and Rb.
CONCLUSION
The abnormal expression of p16 and Rb occurs in DMBA-induced rat ovarian cancer and might be involved in carcinogenesis.

Expression of Cyclin D1, CDK4, p16 and Rb Proteins in Human Soft Tissue Sarcomas.: Jinyoung Yoo, Ah Won Lee, Seok Jin Kang, Byung Kee Kim; Korean J Pathol. 2001;35(3):238-244.

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Abstract PDF: BACKGROUND
Altered cell cycle regulation may underlie the development and/or progression of human malignancies. The purpose of this study is to determine if the oncogenesis of soft tissue sarcomas could be better explained by examining the components involved in G1 phase progression.
METHODS
Sixty-seven soft tissue sarcomas were studied for the immunohistochemical expression of cdk4, cyclin D1, retinoblastoma (Rb) and p16 proteins. For Rb and p16, samples showing either negative or heterogeneous (<80% of tumor cells) staining were considered to be altered.
RESULTS
The cdk4 protein was observed in 64 cases (95.5%). Cyclin D1 was expressed in 14 cases (20.9%). The Rb expression was altered in 48 (71.6%). Sixty-three (94%) sarcomas demonstrated altered p16 expressions. All of the samples displayed altered expressions of either Rb or p16. A high percentage of the tumors with altered Rb were observed in relapsed patients (p<0.05).
CONCLUSIONS
Disturbance in the cell cycle regulatory system involving the Rb/p16/cdk4/cyclin D1 pathway appears to be relatively frequent in soft tissue sarcomas and may play an important role in the tumorigenesis of these tumors. It is noteworthy that the reduced Rb expression correlates with tumor relapse, suggesting its prognostic significance.

Expression of pRb, p16, Cyclin D1 and Cyclin E in Infiltrating Duct Carcinoma of the Breast.: Hea Kyoung Hur, Mee Sook Roh, Jin Sook Jeong, Seo Hee Rha, Gi Yeong Huh, Sook Hee Hong; Korean J Pathol. 2001;35(5):416-423.

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Abstract PDF: BACKGROUND
Inactivation of the retinoblastoma protein (pRb) is a mechanism by which tumor cells can subdue normal growth control. Among the molecules involved in control of pRb phosphorylation, cyclin D1 and cyclin E have been found to be deregulated and overexpressed in various types of cancers.
METHODS
Immunohistochemical stains for pRb, p16, cyclin D1 and cyclin E were performed in 73 cases of infiltrating duct carcinomas of the breast. In addition to analysis of their expression rates, the relationships between their expressions and the clinicopathologic parameters were evaluated.
RESULTS
pRb, p16, cyclin D1 and cyclin E were positive in 64.7% (44 out of 68 cases), 24.6% (15 out of 61 cases), 43.8% (32 out of 73 cases) and 61.6% (45 out of 73 cases), respectively. Their expression rates were not significantly associated with clinicopathologic prognostic factors. 33 out of 38 cases with p16-negative reactions were pRb positive, while 10 out of 15 cases with pRb-negative reactions were p16 positive. There was a significant inverse relationship between pRb and p16 expressions (P<0.005). 25 out of 32 cases with cyclin E-positive reactions were cyclin D1-positive, and 25 out of 45 cases with cyclin D1-positive reactions were cyclin E-positive. A statistically significant association was observed between cyclin D1 and cyclin E expressions (P<0.05).
CONCLUSIONS
The main mechanism during tumorigenesis of breast carcinoma depends on the cyclin D1/p16/pRb pathway, but cyclin E might play a role in the absence of cyclin D1. The inverse correlation between the pRb and p16 expressions may represent one of the important mechanisms in tumorigenesis, as well.

Expression of p16, Rb and FHIT Proteins in Urothelial Carcinoma of the Urinary Bladder.: Sun Hee Han, Ju Han Lee, Seo Hee Kim, Jungsuk An, Eung Seok Lee, Young Sik Kim; Korean J Pathol. 2008;42(5):294-298.

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Abstract PDF: BACKGROUND
The goal of this study was to investigate the expression of p16, retinoblastoma (Rb) and fragile histidine triad (FHIT) proteins in urothelial carcinomas of the urinary bladder, and to evaluate the relationship between clinicopathlogic parameters and each protein expression level. METHODS: The expression of p16, Rb, and FHIT proteins were studied in 176 patients with urothelial carcinoma of the urinary bladder by immunohistochemistry. RESULTS: The diffuse positive expression of the p16 protein was significantly associated with high grade and advanced tumor depth (p=0.007 and p=0.020). The loss of the Rb protein was significantly associated with old age and disease recurrence (p=0.020 and 0.037). The loss of the FHIT protein was significantly associated with advanced tumor depth (p=0.002). CONCLUSION: Our data suggest that p16 and FHIT proteins may be involved in the progression of urothelial carcinoma. In addition, p16 may be a useful prognostic marker for individual urothelial carcinoma patients.

A Histopathological Analysis on 73 Cases of Enucleated Eyeballs.: Kyoung Chan Choi, Joon Hyuk Choi, Won Hee Choi, Tae Sook Lee, Myung Mi Kim; Korean J Pathol. 1994;28(5):460-468.

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Abstract PDF: A total of 73 enucleated eyeballs is reviewed and analyzed clinicopthologically. These eyeballs were selected among the enucleated spceimens that had been removed at the Yeungnam University Hospital during a period of 10 years beginning from 1983 to 1992. Following results were obtained. 1) When the eyeballs were classified according to me direct cause of removal, the neoplasm was the most common single cause accounting for 26 cases(35.6%) out of 73 cases, followed by phthisis bulbi l6 cases(21.9%), trauma 10 cases(13.7%), glaucoma 8 cases(10.9%), inflammation 5 cases(6.8%), staphyloma 4 cases(5.5%), retinal detachment 1 cases(1.4%), Coat's disease 1 cases(1.4%), corneal disease 1 cases(1.4%) and choroidal hemorrhage 1 cases(1.4%). 2) 39 cases(53.4%) were male and 34(46.6%) were female. 23 cases(31.5%) were below 10 years of age, which was the highest rate. 3) The neoplastic lesion included retinoblastoma 20 cases(76.9%) in 26 neoplasms, malignant melanoma 4 cases(15.3%), hemagioblastoma of optic disc 1 cases(3.9%), adenocarcinoma of Meibomian gland 1 cases(3.9%). 4) Retinoblastoma was the commonest intraocular tumor accounting for 20 out of 26 cases, In growth pattern, 80.0% of the tumor grew endophtytically. True rosette were seen 60% of the retinoblastoma.

A Histopathologic Study of Mammary Dysplasia.: Je G Chi, Chul Woo Kim, Yeon Lim Suh; Korean J Pathol. 1988;22(2):123-130.

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Abstract PDF: "Mammary dysplasia" and "fibroadenoma" represent almost all benign breast disease presenting with breast lumps. Mammary dysplasia comprises variable non-specific changes of stroma and epithelium, but fibroadenoma has been classified as a benign neoplasm, although both features not uncommonly coexist. Authors performed a blind microscopic review of 660 cases of benign breast lesions and the results are as followings. 1. Only 27.9% of all cases consisted of pure fibroadenoma in contrast to 57.5% in the original diagnosis. 2. Fibrocystic disease frequently contained foci of fibroadenoma showing varied stages (68.3%), and the younger age group presented more wide areas of fibroadenoma. 3. The most common feature of the fibrocystic disease was fibrosis, followed by cystic change, adenosis and epithelial hyperplasia in order of frequency. 4. Fibroadenoma may be a form of a spectrum produced by hormonal imbalance, and better classified as a nonneoplastic lesion.

Spinal Fluid Cytology of Retinoblastoma.: Je G Chi, Chul Woo Kim, Yeon Lim Suh; Korean J Pathol. 1988;22(2):123-130.

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Abstract PDF: Of all the primary central nervous system tumors, the medulloblastoma, glioblastoma multiforme, ependymoma and pineal germinoma tend to exfoliate in the cerebrospinal space. With all other types of the tumor, abnormal cells may seldom be definitely identified in the cerebrospinal fluid. Up to now the tumor cells have been rarely found in CSF cases of retinoblastoma. We have experienced a case of advanced retinoblastoma that showed exfoliated cells in spinal fluid.

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