Cancer Research and Treatment

Original Articles

Correlation of AR, EGFR, and HER2 Expression Levels in Prostate Cancer: Immunohistochemical Analysis and Chromogenic In Situ Hybridization: Kwang Hyun Baek, Min Eui Hong, Yoon Yang Jung, Chung Hun Lee, Tae Jin Lee, Eon Sub Park, Mi Kyung Kim, Jae Hyung Yoo, Soo Whan Lee; Cancer Res Treat. 2012;44(1):50-56. Published online March 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.1.50

PURPOSE
The androgen receptor (AR) plays a central role in prostate cancer. Evidence from several groups indicates that epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) may enhance AR activity in prostate cancer cell lines. This study was designed to investigate the protein expression of AR, EGFR, and HER2 and to determine whether the EGFR and HER2 genes are amplified in prostate cancer tissues.
MATERIALS AND METHODS
The protein expression levels of AR, EGFR, and HER2 in a tissue microarray block of 66 prostate cancer samples were investigated by immunohistochemical analysis and chromogenic in situ hybridization was used to determine whether the EGFR and HER2 genes were amplified in these tissues.
RESULTS
The AR and EGFR proteins were expressed in 59.1% and 40.9% of prostate cancers, respectively, but their expression levels were not significantly associated with clinicopathologic factors. Of the cases in which tissues were negative for EGFR protein expression, 69.2% were positive for AR protein expression; however, AR protein expression was significantly reduced (44.4%) in tissues in which EGFR protein was expressed. HER2 expression was detected in only 1 case (1.5%). No amplification of the EGFR or HER2 genes was found in prostate cancer specimens.
CONCLUSION
This study was limited by small number of subjects, but it can still be inferred that the expression levels of the AR and EGFR proteins are inversely correlated in prostate cancer patients. The potential utility of EGFR and HER2 as prognostic factors or therapeutic targets warrants further study.

Citations

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Mast Cell and Macrophage Counts and Microvessel Density in Invasive Breast Carcinoma-Comparison Analysis with Clinicopathological Parameters: Gui Young Kwon, Sang Dae Lee, Eon Sub Park; Cancer Res Treat. 2005;37(2):103-108. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.103

Abstract PDF PubReader ePub

Purpose

The purpose of this study was to evaluate the clinicopathological significance of the microvessel density and macrophage and mast cell counts in invasive breast carcinomas.

Materials and Methods

45 invasive breast carcinomas were immunohistochemically stained with the endothelial antigen, CD34, and macrophage marker, CD68. 0.1% toluidine blue was used to highlight mast cells. The microvessel and mast cell counts were performed at ×200 magnification and the macrophages at ×400 magnification.

Results

With the 45 invasive breast carcinomas, there were no statistically significant associations between the mast cell, macrophage and microvessel counts and the tumor size and lymph node status. ER and PR negative mast cells infiltrated more than in cases of positive stati, with statistical significance (p-value=0.010 and 0.005, respectively). The macrophage counts were negatively correlated with the PR status (p-value=0.030). With respect to the c-erbB-2 status, there was no significance correlation with the mast cell, macrophage and microvessel counts. The mast cell counts showed significantly positive correlation with the microvessel counts in the invasive breast carcinomas (p-value=0.015). In a comparison of the macrophage counts with the microvessel counts, a positive tendency for both parameters, but without statistical significance (p-value=0.310).

Conclusion

Increasing numbers of mast cells and macrophages were recruited in invasive breast carcinomas, which contribute to angiogenesis. The microvessel density in invasive breast carcinomas had no statistically significant association with the tumor size, lymph node status, and histological grade, presence of DCIS component, estrogen/progesterone receptor status and cerbB-2 status. The evaluation of angiogenesis using these methods is not thought to provide an independent clinicopathological factor in invasive breast carcinomas.

Citations

Citations to this article as recorded by

Correlation of microvessel density with histopathological parameters of carcinoma breast
Aditi V. Goyal, Samarth Shukla, Sourya Acharya, Sunita Vagha, Suhas Jajoo
Indian Journal of Medical Research.2023; 158(4): 417. CrossRef
Study of microvessel density in breast carcinoma with CD34 immunostaining – An institutional experience in Puducherry
Vigneswaramoorthi Vinayagamoorthi, Erli Amel Ivan, G. Revathi, V. Sriram, Ramya Gandhi, Reenaa Mohan, Roy Arokiam
Journal of Current Research in Scientific Medicine.2023; 9(2): 93. CrossRef
Few, but Efficient: The Role of Mast Cells in Breast Cancer and Other Solid Tumors
Maria Teresa Majorini, Mario Paolo Colombo, Daniele Lecis
Cancer Research.2022; 82(8): 1439. CrossRef
Quantitative mast cell analysis and hormone receptor study (ER, PR and HER2/neu) in invasive carcinoma of breast
RamaD Pyla, RM Potekar, VijayalaxmiS Patil, AnilK Reddy, KV Sathyashree
Indian Journal of Pathology and Microbiology.2020; 63(2): 200. CrossRef
Tumor associated mast cells: biological roles and therapeutic applications
Shikha Saxena, Anil Singh, Priyanka Singh
Anatomy & Cell Biology.2020; 53(3): 245. CrossRef
Serum uPAR as Biomarker in Breast Cancer Recurrence: A Mathematical Model
Wenrui Hao, Avner Friedman, Yi-Hsien Hsieh
PLOS ONE.2016; 11(4): e0153508. CrossRef
Genomic alterations and phenotype of large compared to small high-grade ductal carcinoma in situ
E. Shelley Hwang, Aseem Lal, Yunn-Yi Chen, Sandy DeVries, Rebecca Swain, Joe Anderson, Ritu Roy, Frederic M. Waldman
Human Pathology.2011; 42(10): 1467. CrossRef

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Expression of MDM-2 and p53 Proteins in Gastric Adendegrees Carcinoma and Its Relationship with Clinicopathologic Factors: Ji Woong Yang, Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyoung Yoo; J Korean Cancer Assoc. 2000;32(3):476-486.

Abstract PDF: PURPOSE
MDM-2 is an oncoprotein that inhibits p53 tumor-suppressor protein. These abnor malities have a role in tumorigenesis through inactivation of p53 function. To determine the clini copathological and prognostic value of MDM2 abnormalities in gastric adendegrees Carcinoma, MDM-2& p53 protein expression were analysed in surgically resected materials of gastric adendegrees Carcinoma.
MATERIALS AND METHODS
Fifty cases which had got follow-up after surgical resection were immunohistdegrees Chemically studied with p53 and MDM-2 antibodies. We defined variable clinico pathologic factors for expression of p53 and MDM-2 protein and analysed their relationships.
RESULTS
Immunohistdegrees Chemical stain revealed expression of MDM-2 protein as a 52.0% (26/50) and p53 protein 20.0% (10/50), respectively. But their expressions were not assdegrees Ciated with clinicopathological factors such as T-factor, N-factor, stage, histology and differentiation. Overall, p53-negative patients seemed to have a better prognosis regardless of MDM-2 protein status (P= 0.057). MDM-2 protein status was considered to have no play as a prognostic factor.
CONCLUSION
In the gastric adendegrees Carcinoma, p53 protein expression seemed to have a inverse relationship with clinical outcomes but MDM-2 protein expression, which was observed more frequently than those of p53, seemed not to be prognostic indicator.

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Expression of Prostatic Carcinoma Oncogene PTI - 1 in Prostatic Carcinoma , Prostatic Intraepithelial Neoplasia and Benign Prostatic Hyperplasia Using in situ PCR: Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; J Korean Cancer Assoc. 2000;32(1):136-147.

Abstract PDF: PURPOSE
Prostatic tumor induced gene-1 (PTI-1) is a mutated human EF-la and putative prostatic carcinoma tumor-inducing oncogene, that is differently expressed in prostatic cancer and benign prostatic hyperplasia. And, it is more sensitive marker than prostate- specific antigen (PSA) for detecting human prostate cancer in the bloodstream. This study invastigated the expression of PTI-1 in paraffin embedded tissue of prostatic carcinoma, prostatic intraepithelial neoplasia, and benign prostatic hyperplasia using in situ PCR.
MATERIALS AND METHODS
we evaluated expression of PTI-1 in prostatic carcinoma with prostatic intraepithelial neoplasia (PIN) of 32 cases, benign hyperplasia of 20 cases, high grade transitional cell carcinoma of 10 cases and colon cancer of 10 cases for control group. Also, the immunohistochemical staining for PSA was performed to comparison with clinical value of PSA.
RESULTS
The serum level of PSA was closely related to stage and Gleason score (p < 0.05). However, the results of immunohistochemical stains were variable to stage and Gleason score. PTI-1 using in situ PCR expressed in 50% of prostatic carcinoma, 41% of prostatic intraepithelial neoplasia, 10% of benign hyperplasia and colon cancer (p < 0.05). No expression is observed in transitional cell carcinoma. In prostatic carcinoma, PTI-1 expressed in 43.8% (7/16) of stage II, 50.0% (5/10) of stage III, and 66.7% (4/6) of stage IV (p<0.05). In PIN, expression of PTI-1 was similar to prostatic carcinoma (p<0.05).
CONCLUSION
PTI-1 represented a relatively sensitive marker for prostatic carcinoma and PIN, indicator of prostatic carcinoma progression.

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Immunohistochemical Analysis of MHC Class 2 (HLA-DR / DP), ICAM-1, CD68(+) Macrophage Expression in Gastric Adenocarcinoma: Eon Sub Park, Seong Nam Kim, Tae Jin Lee, Im Joong Yoon, Yong Kyoo Shin, Jae Hyung Yoo; J Korean Cancer Assoc. 1998;30(1):40-54.

Abstract PDF: PURPOSE
Gastric adenocarcinoma is the most common malignant tumor in Korea and immunochemotherapy can be alternative method of the treatment for it. So we evaluated several immunologic markers, Major Histocomatibility (MHC) Antigen and Intercellular Adhesion Molecule (ICAM)-1 which play an important roles in cellular immune response of the host to the tumar cells, HLA-DR/DP antigens, one of the MHC class II which is expressed in various conditions, CD 68 antigen which are also important factor in immune response to the tumor cells.
MATERIALS AND METHODS
We compared the expression of MHC class II (HLA-DR/DP) antigens, ICAM-1 and the number of tumor-infiltrating macrophages presenting CD68 antigen in formalin-fixed paraffin-embedded tissue sections of 95 gastric adenocarcinomas using immunohistochemistry. In addition to analyze the relationship between expression of these antigens in gastric adenocarcinoma, histolopathologic findings such as tumor invasion, regional lymph node metastasis and histologic differentiation are evaluated.
RESULTS
The rate of HLA-DR/DP expression was 60% and strongly associated with tumor differentiation, invasion and regional lymph node metastasis. ICAM-1 was expressed in 15% and slightly increased in well-differentiated carcinoma. The lack of expression of ICAM-1 was observed in high invasive tumor (T 4). CD 68(+) macrophages counts were significantly increased in around the tumor cells, compared to normal epithelia. HLA-DR/DP expression and infiltrating CD 68(+) macrophage numbers were significantly associated (p<0.05), but there was no correlationship between ICAM-1 and CD 68(+) macrophage numbers.
CONCLUSION
It was considered that enhanced expression of HLA-DR/DP antigens, ICAM-1 and CD68(+) macrophages in gastric adenocarcinomas may be an immunophenotypic deviation. HLA-DR/DP and CD68(+) macrophages infiltration showed correlationship with tumor invasion and regional lymph node metastasis, that they may be used as a prognostic factor of the tumor growth.

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Effects of Combination Chemotherapy Depending on The Expression of Neuron Specific Enolase (NSE), P-Glycoprotein (PgP) and Glutathione S-Transferase (GST)-pai in Advanced Non-Small Cell Lung Cancer: Chul Won Jung, Jong Wook Shin, Sang Jae Lee, Eon Sub Park; J Korean Cancer Assoc. 1997;29(2):189-197.

Abstract PDF: PURPOSE
Neuroendocrine differentiation and expression of drug resistance may affect the response to chemotherapy and the prognosis of advanced non-small cell lung cancer. We conducted retrospective study to evaluate the possibilities of neuroendocrine differentiation and drug resistance markers being used as prognostic factors in patients with non-small cell lung cancer. MATERIAL AND METHOD: Immunohistochemical staining of NSE, PgP and GST-pai with polyclonal antibodies in pathologic specimens of 47 patients with non-small cell lung cancer were done. The relationship between the expression of the markers and the response to cisplatin-based chemotherapy and the overall survival were assessed.
RESULTS
NSE staining was positive in 17% and there was no difference between adenocarcinoma and squamous cell carcinoma. NSE positive patients showed increased response rate (63% vs 26%, p=0.049) and prolonged response duration (15.8mo vs 4.5mo, p=0.0007). But there was no difference in overall survival between NSE positive and negative groups. The PgP positive rate was 17% and GST-pai positive rate was 47%. No correlations were found among the expression of drug resistance, the sensitivity to chemotherapy and overall survival.
CONCLUSION
Patients with non-small cell lung cancer with positive NSE showed increased response rate to chemotherapy and prolonged response duration but overall survival was not related to NSE expression. Expression of PgP and GST- were not important in predicting the prognosis in non-small cell lung cancer.

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In Vitro Chemosensitivaty Test of SK-302 on Human Gastric Carcinoma Cell Lines: Soo Kie Kim, Woon Seob Shin, Yoon Sun Park, Sun Ju Choi, Kyung Ho Lee, Joo Young Park, Choon Myung Koh, Chan Mug Ahn, Weon Sub Park; J Korean Cancer Assoc. 1995;27(5):703-711.

Abstract PDF: SK-30ZB with quinomycin-related structure is considered to be potent antitumor antibiotic. There were several reports that quinomycins and their derivatives showed wide spectrum of anti-tumor activity. But there were no reports on anti-gastric tumor activity. We fould SK- 302B with anti-gastric tumor activity in vitro using our established anti-tumorsubstance screening system. Recent attention has been focused on the possibility of predicting the effectiveness of anti-cancer drugs on individual tumor through chemosensitivity tests. However, optimal conditions for in vitro chemosensitivity test on human gastric carcinoma cell lines were not well established. We attempted to establish optimal conditions and to evaluate compara- tively in vitro tumor cell cytotoxicity between SK-302B and adriamycin, using 7 human gastric carcinoma celi lines. The optimal cell number and culture duration for in vitro tumor cell cytotoxicity(TCC) and colony formation inhibition assay(CFIA) is 5x10(3) - 1x10(4) cells/well (TCC) and 2.510(3) - 10(3) cells/well(CFIA), 4 days(TCC) and 10 - l4 days(CFIA), respectively, for all gestric cancer cell lines. Under these conditions, we performed chemosensitivity test. Measurement of cytotoxicity(IC50) and colony forming efficiency revealed higher tumoricidal activity of SK-302 B against all tested gastric cancer cell lines than compared to that of adriamycin. In conclusion, we preseneted optimal conditions for in vitro chemosensitivity test on human gastric carcinoma cell lines. Using optimal conditions of this sytem, it could be demonstrated that SK-302B exerted a potent gastric cancer cell growth inhibition in vitro. Therefor, These data suggest that SK-302B may have a possibility of development as promising candidate of anti-gastric cancer chemotherapeutic agent.

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Immunohistochemical Analysis of Transforming Growth Factor - β Isoforms ( TGF-β1 , TGF-β2 , TGF-β3 ) Expression in Gastric Adenocarcinoma: Jae Hyung Yoo, Weon Sub Park, Mi Kyung Kim, Tae Jin Lee, Sang Jun Lee; J Korean Cancer Assoc. 1996;28(6):1040-1050.

Abstract PDF: Immunohistochemical studies using polyclonal antibodies to transforming growth factor beta isoforms(TGF-￥a1, TGF-￥a2 & TGF-￥a3), a multifunctional regulatory proteins which hoave effects on normal and transformed cells, were performed on 66 cases of gastric adenocarcinomas in order to analyze the relationship between expression of these isoforms in gastric cancer cells, adjacent mucosa of the cancer and normal control gastric mucosa. In addition to determine the relationship between expression of TGF-￥a isoforms and various clinicopathological states, including tumor location, histologic types, regional lymph node metastasis and depth of invasion of tumors were carried out. The positive staining reactivity was detected within the cytoplasm and on the cell membrane. The rate of TGF-￥a isoforms expression in gastric adenocarcinomas were 47% in TGF-￥a1, 83% in TGF-￥a2, and 27% in TGF-3, respectively. The adjacent gastric mucosa from adenocarcinomas and normal control mucosa were 40 % in TGF-￥a1, 40% and 55% in TGF-￥a2, 20% and 33% in TGF-￥a3, respectively. Among the TGF-￥a isoforms, TGF-￥a2 was strongly associated with histologic differentiation and regional lymph node metastasis. No significant association was found between expression of TGF-￥a isoforms and tumor location, histologic types and T-stages. From these results, we can postulate that the altered expression of TGF-￥a isoforms, especially TGF-￥a2, play an important role in histogenesis and gastric cancer progression and regional lymph node metastasis.

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