Journal of Pathology and Translational Medicine

Original Articles

Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets: Jeong Hwan Park, Su-Jin Shin, Hyun-Jung Kim, Sohee Oh, Yong Mee Cho; J Pathol Transl Med. 2024;58(6):321-330. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.31

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Abstract PDF: Background
Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms
Methods
We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets.
Results
We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063).
Conclusions
Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms: Ji Hyun Lee, Hye Ju Kang, Chong Woo Yoo, Weon Seo Park, Jun Sun Ryu, Yuh-Seog Jung, Sung Weon Choi, Joo Yong Park, Nayoung Han; J Pathol Transl Med. 2019;53(1):23-30. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.12

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Background
Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues.
Methods
A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays.
Results
Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology.
Conclusions
PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.

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Expression of c-MET in Invasive Meningioma: Sumi Yun, Jae Moon Koh, Kyu Sang Lee, An Na Seo, Kyung Han Nam, Gheeyoung Choe; J Pathol Transl Med. 2015;49(1):44-51. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.13

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Abstract PDF

Background
Meningiomas show high recurrence rates even after curative tumor removal. The invasiveness of meningiomas may contribute to their high recurrence rates. Recently, c-MET and hepatocyte growth factor (HGF) have been reported to be involved in cancer invasion. Methods: We examined the immunohistochemical expression of c-MET and HGF in 100 cases of patients with meningiomas who have undergone complete tumor removal. Results: c-MET^-High and HGFHigh were found in 17% and 13% of meningiomas, respectively. Brain invasion was observed in 17.6% of c-MET^-High meningiomas, but in only 2.4% of c-MET^-Low meningiomas (p=.033). Bone/ soft tissue invasion was observed in 23.5% of c-MET^-High meningiomas and in 9.6% of c-MET^-Low meningiomas (p=.119). HGF^-High did not show statistical association with brain invasion or bone/ soft tissue invasion. c-MET^-High demonstrated shorter recurrence-free survival (RFS, 93.5±8.2 months vs 96.1±1.9 months); however, this difference was not statistically significant (p=.139). There was no association of HGF^-High with RFS. Conclusions: This study demonstrates that c- MET^-High is associated with brain invasion of meningiomas, and that c-MET expression may be a useful predictive marker for meningioma recurrence. Patients with invasive meningiomas with high expressions of c-MET may be good candidates for targeted therapy using c-MET inhibitors.

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Case Study

Anaplastic Transformation of Papillary Thyroid Carcinoma in a Young Man: A Case Study with Immunohistochemical and BRAF Analysis: Ji Hye Park, Hyeong Ju Kwon, Cheong Soo Park, SoonWon Hong; Korean J Pathol. 2014;48(3):234-240. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.234

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Abstract PDF

This study reports a case of anaplastic transformation from a well-differentiated thyroid carcinoma in a young patient. The first recurrent tissue contained poorly differentiated foci that revealed lower thyroglobulin, thyroid transcription factor 1 (TTF-1), and galectin-3 expression than the well-differentiated area. However there was no increased p53 or Ki-67 expression in the poorly differentiated foci, nor in the well-differentiated area. The tissue subsequently relapsed and revealed only anaplastic features, complete loss of thyroglobulin, TTF-1, and galectin-3 expression and revealed an increase in p53 and Ki-67 expression. The BRAF V600E and BRAF V600V mutation were found in the initially diagnosed papillary thyroid carcinoma and the poorly differentiated foci of the recurring papillary thyroid carcinoma; however, only the BRAF V600V mutation was found in the anaplastic carcinoma. These results suggest that overexpression of p53 and Ki-67 contributed to the anaplastic transformation. We also found that the BRAF type changed during the tumor relapse.

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Original Articles

Evaluation of Protein Expression in Housekeeping Genes across Multiple Tissues in Rats: Hye Jeong Kim, Jong In Na, Byung Woo Min, Joo Young Na, Kyung Hwa Lee, Jae Hyuk Lee, Young Jik Lee, Hyung Seok Kim, Jong Tae Park; Korean J Pathol. 2014;48(3):193-200. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.193

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Abstract PDF

Background

Housekeeping genes, which show constant protein expression patterns between different tissue types, are very important in molecular biological studies as an internal control for protein research.

Methods

The protein expression profiles of seven housekeeping genes (HPRT1, PPIA, GYS1, TBP, YWHAZ, GAPDH and ACTB) in various rat tissues (cerebrum, cerebellum, cardiac ventricle and atrium, psoas muscle, femoral muscle, liver, spleen, kidney, and aorta) were analyzed by Western blot and compared by coefficient of variation (CV).

Results

HPRT1 was stably expressed (CV≤10%) in six tissues (cerebrum, cerebellum, ventricle, femoral muscle, spleen, and kidney), PPIA was stably expressed in five tissues (cerebrum, cerebellum, ventricle, spleen and kidney), YWHAZ was stably expressed in three tissues (cerebrum, cerebellum, and kidney), and GAPDH was stably expressed in four tissues (cerebrum, ventricle, psoas muscle, and kidney). In comparison, GYS1, TBP, and ACTB were found to have CV values over 10% in all tissues. Of the seven genes examined, four (HPRT1, PPIA, YWHAZ, and GAPDH) were found to be stably expressed across multiple organs, with low CV values (≤10%).

Conclusions

These results will provide fundamental information regarding internal controls for protein expression studies and can be used for analysis of postmortem protein degradation patterns in forensic medicine.

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Microtubule-Associated Protein Tau, α-Tubulin and βIII-Tubulin Expression in Breast Cancer: Soyoung Im, Changyoung Yoo, Ji-Han Jung, Ye-Won Jeon, Young Jin Suh, Youn Soo Lee, Hyun Joo Choi; Korean J Pathol. 2013;47(6):534-540. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.534

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Abstract PDF

Background

The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment.

Methods

Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival.

Results

Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049).

Conclusions

Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

Citations

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Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche
Tessy Thomas Maliekal, Dhrishya Dharmapal, Suparna Sengupta
Frontiers in Immunology.2022;[Epub] CrossRef
RAD6 inhibition enhances paclitaxel sensitivity of triple negative breast cancer cells by aggravating mitotic spindle damage
Brittany M. Haynes, Kristen Cunningham, Malathy P. V. Shekhar
BMC Cancer.2022;[Epub] CrossRef
Influence of Paclitaxel and Doxorubicin Therapy of ßIII-Tubulin, Carbonic Anhydrase IX, and Survivin in Chemically Induced Breast Cancer in Female Rat
Alena Pastornická, Silvia Rybárová, Slávka Drahošová, Jozef Mihalik, Andrea Kreheľová, Andriana Pavliuk-Karachevtseva, Ingrid Hodorová
International Journal of Molecular Sciences.2021; 22(12): 6363. CrossRef
Intelligently thermoresponsive flower-like hollow nano-ruthenium system for sustained release of nerve growth factor to inhibit hyperphosphorylation of tau and neuronal damage for the treatment of Alzheimer's disease
Hui Zhou, Youcong Gong, Yanan Liu, Anlian Huang, Xufeng Zhu, Jiawei Liu, Guanglong Yuan, Li Zhang, Ji-an Wei, Jie Liu
Biomaterials.2020; 237: 119822. CrossRef
HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells
J. R. Ribeiro, C. Schorl, N. Yano, N. Romano, K. K. Kim, R. K. Singh, R. G. Moore
Journal of Ovarian Research.2016;[Epub] CrossRef
A strategy to identify housekeeping genes suitable for analysis in breast cancer diseases
Tatiana M. Tilli, Cláudio da Silva Castro, Jack A. Tuszynski, Nicolas Carels
BMC Genomics.2016;[Epub] CrossRef
Increased expression of αTubulin is associated with poor prognosis in patients with pancreatic cancer after surgical resection
Chao Lin, Guo-chao Zhao, Ya-dong Xu, Dan-song Wang, Da-yong Jin, Yuan Ji, Wen-hui Lou, Wen-chuan Wu
Oncotarget.2016; 7(37): 60657. CrossRef
Oblongifolin C inhibits metastasis by up-regulating keratin 18 and tubulins
Xiaoyu Wang, Yuanzhi Lao, Naihan Xu, Zhichao Xi, Man Wu, Hua Wang, Xiyi Li, Hongsheng Tan, Menghong Sun, Hongxi Xu
Scientific Reports.2015;[Epub] CrossRef
Regulation of human MAPT gene expression
Marie-Laure Caillet-Boudin, Luc Buée, Nicolas Sergeant, Bruno Lefebvre
Molecular Neurodegeneration.2015;[Epub] CrossRef

Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma: Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Wonkyung Jung, Eunjung Lee, Bong Kyung Shin, Aeree Kim, Han Kyeom Kim, Baek-hui Kim; Korean J Pathol. 2013;47(3):219-226. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.219

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Abstract PDF

Background

Overexpression of heat shock protein 70 (HSP70) has been observed in many types of cancer including gastric adenocarcinomas, although the exact role of HSP70 in carcinogenesis remains unclear.

Methods

The study analyzed a total of 458 radical gastrectomy specimens which were immunohistochemically stained with HSP70, p53, and Ki-67 antibodies.

Results

The study determined that the expression of HSP70 was significantly increased in early gastric cancer (EGC) compared to advanced gastric cancer (p<0.001). The HSP70 expression was correlated with well-differentiated tumor type, intestinal type of Lauren classification and the lower pT and pN stage. Negative expression of Ki-67 and p53 expression was associated with poor prognosis. The study did not find any correlation between HSP70 and p53 expression. The study determined that HSP70 expression in the EGC subgroup was associated with a poor prognosis (p=0.009), as well as negative Ki-67 expression (p=0.006), but was not associated with p53. Based on multivariate analysis, HSP70 expression (p=0.024), negative expression of Ki-67, invasion depth and lymph node metastasis were determined to be independent prognostic markers.

Conclusions

HSP70 is expressed in the early stages of gastric adenocarcinoma. In EGC, HSP70 is a poor independent prognostic marker and is correlated with a low proliferation index.

Citations

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The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis
Xiaolu Wang, Li Xie, Lijing Zhu
BMC Gastroenterology.2021;[Epub] CrossRef
Beta-sheet-specific interactions with heat shock proteins define a mechanism of delayed tumor cell death in response to HAMLET
Aftab Nadeem, James C.S. Ho, Tuan Hiep Tran, Sanchari Paul, Victoria Granqvist, Nadege Despretz, Catharina Svanborg
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Shubhi Srivastava, Vinaya Vishwanathan, Abhijit Birje, Devanjan Sinha, Patrick D’Silva
Critical Reviews in Biochemistry and Molecular Biology.2019; 54(6): 517. CrossRef
Clinicopathologic significance and prognostic value of Ki-67 expression in patients with gastric cancer: a meta-analysis
Guanying Luo, Yunzhao Hu, Zhiqiao Zhang, Peng Wang, Zhaowen Luo, Jinxin Lin, Canchang Cheng, You Yang
Oncotarget.2017; 8(30): 50273. CrossRef
Extracellular HSP70-peptide complexes promote the proliferation of hepatocellular carcinoma cells via TLR2/4/JNK1/2MAPK pathway
Yi Zhe, Yan Li, Dan Liu, Dong-Ming Su, Jin-Gang Liu, Hang-Yu Li
Tumor Biology.2016; 37(10): 13951. CrossRef
The cytomegalovirus protein UL138 induces apoptosis of gastric cancer cells by binding to heat shock protein 70
Wenjing Chen, Kezhi Lin, Liang Zhang, Gangqiang Guo, Xiangwei Sun, Jing Chen, Lulu Ye, Sisi Ye, Chenchen Mao, Jianfeng Xu, Lifang Zhang, Lubin Jiang, Xian Shen, Xiangyang Xue
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Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis
J Gong, D Weng, T Eguchi, A Murshid, M Y Sherman, B Song, S K Calderwood
Oncogene.2015; 34(43): 5460. CrossRef

Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival: Soyoung Im, Hyun Joo Choi, Changyoung Yoo, Ji-Han Jung, Ye-Won Jeon, Young Jin Suh, Chang Suk Kang; Korean J Pathol. 2013;47(2):116-123. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.116

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Abstract PDF

Background

The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established.

Methods

Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically.

Results

The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012).

Conclusions

Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

Citations

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Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients
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Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma: Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim; Korean J Pathol. 2012;46(6):515-522. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515

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Abstract PDF

Background

Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).

Methods

Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by in situ hybridization and amplification of the c-Met gene by fluorescence in situ hybridization.

Results

The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.

Conclusions

Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.

Citations

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Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma.: Kyung Hwa Lee, Soong Lee, Hyeon Min Lee, Seung Chul Back, Sung Bum Cho, Jae Hyuk Lee; Korean J Pathol. 2011;45(4):397-405.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.397

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Abstract PDF

BACKGROUND
The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance.
METHODS
Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method.
RESULTS
Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041).
CONCLUSIONS
Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

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A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer
Pierina Cetraro, Julio Plaza-Diaz, Alex MacKenzie, Francisco Abadía-Molina
Cancers.2022; 14(7): 1671. CrossRef

Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.: Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee; Korean J Pathol. 2010;44(3):252-258.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252

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Abstract PDF

BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.

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Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef
The Relationship Between Estrogen/Progesterone Receptor and Expression of mTOR/pAkt Proteins and the Analysis of Prognosis in Breast Cancer
Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
Journal of Breast Disease.2013; 1(1): 8. CrossRef
Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef

The Expression of Apolipoprotein D in Hepatocellular Carcinoma.: Hongxiu Han, Chan Kum Park; Korean J Pathol. 2010;44(2):187-190.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.187

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Abstract PDF: BACKGROUND
Apolipoprotein D (Apo D) has recently been identified as a novel tumor suppressor gene. Apo D may have a profound effect on the carcinogenesis and progression of hepatocellular carcinoma. This study was designed to evaluate the expression of Apo D in hepatocellular carcinoma and to investigate the relationship between the expression of Apo D and the clinicopathological characteristics and the patients' survival.
METHODS
An immunohistochemical study was performed on the tumors and tissues from 43 hepatocellular carcinoma (HCC) patients with controls to determine the expression of Apo D protein.
RESULTS
Our data showed that a higher expression of Apo D was seen in 10 of 43 cases (23.3%), while a lower and no expression of Apo D was observed in 28 of 43 cases (65.1%) and 5 of 43 cases (11.6%), respectively. A reduced expression of Apo D was correlated with the tumor stage (p = 0.037) and tumor size (p = 0.017). However, the patients' 5-year survival was not associated with the expression of Apo D (p = 0.903).
CONCLUSIONS
The results suggest that a reduced Apo D protein expression may play an important role in HCC progression as associated with the tumor stage and size, but it does not affect the survival of HCC patients.

KIT/PDGFRA Expression and Mutation in Testicular Seminoma and Ovarian Dysgerminoma.: Song Yi Choi, Kwang Sun Suh, Yong Beom Kim, Hyun Jeong Lee, Eun Sun Kim, Mee Ja Park; Korean J Pathol. 2009;43(6):528-534.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.528

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Abstract PDF

BACKGROUND
KIT and PDGFRA are tyrosine kinase receptors. Stem cell factor/KIT-mediated signaling plays a role in normal spermatogenesis, and the alteration of KIT is important in the pathogenesis of seminomas/dysgerminomas (SD). METHODS: To determine the role of expression and mutation of the KIT and PDGFRA genes, we analyzed 16 seminoma cases, 4 spermatocytic seminoma (SS) cases and 8 dysgerminoma cases for KIT and PDGFRA expression and mutation of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR-SSCP methods. RESULTS: KIT was immunohistochemically positive in all 24 SD cases, and one of four (25%) SS cases. PDGFRA was immunohistochemically evident in 16 of the 24 (66.6%) SD cases, and two of the four (50%) SS cases. KIT expression was significantly reduced in SS compared with seminoma (p=0.0035). Four cases (14.3%) displayed mutation in KIT exon 17 or PDGFRA exon 12. Distant metastasis was present in three cases (10.7%), one of which had a nonsense mutation in KIT. CONCLUSIONS: These results indicate that KIT is expressed in the majority of SD cases, but not in most SS cases. However, there was no significant correlation between the clinicopathologic features and mutation or expression of KIT and PDGFRA.

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Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors
Sung Hee Jung, Kwang Sun Suh, Dae Young Kang, Dong Wook Kang, Young-Beum Kim, Eun-Sun Kim
Gut and Liver.2011; 5(2): 171. CrossRef

Cytoskeletal Changes in Cortical Dysplasia.: Min Young Lee, Jae Hun Chung, Young Jong Woo, Hyoung Ihl Kim, Min Cheol Lee; Korean J Pathol. 2000;34(4):300-309.

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Abstract PDF: Cortical dysplasia is a cause of intractable epilepsy and a candidate for surgical resection to control epileptic attacks. The neuronal cytomegaly and balloon cell change are the diagnostic hallmarks of cortical dysplasia. Little research has been performed about the normal-sized dysplastic neuron which has complex arborizing dendrites and lacks in its polarity. The aim of this study was to define the histopathologic characteristics of the neurons in cortical dysplasia. Twelve cases of cortical dysplasia who underwent partial lobectomy for intractable seizures were selected and immunohistochemical staining for NF-M/H, MAP2, tau, and ubiquitin was performed. The perikarya and dendrite of dysplastic neurons were more intensely labeled with antibodies for the high and medium molecular weight neurofilament proteins (NF-M/H) than normal neurons. Immunoreactivity with the MAP2 antibody expressed mainly within the somatodendritic regions was present in the dysplastic or normal neurons without any significant difference in intensity. The complex arborizing dendrites of dysplastic neurons were easily identified due to pronounced immunoreactivity within the somatodendritic regions. Immunoreactivity with the primary antibody against tau and ubiquitin was present in the normal-looking neurons as well as the dysplastic neurons. This study suggests that the dysplastic neurons in cortical dysplasia are accompanied by changes of cytoskeletal neurofilaments, and the immunohistochemical stains for NF-M/H, MAP2, tau, and ubiquigin are useful to detect them.

Expressions of MAGE-3, PCNA, p21, and p53 Proteins in the Hypopharyngeal Squamous Cell Carcinoma Cell Line (PNUH-12) Analysed by Bivariate Flow Cytometry.: Hee Kyung Chang, Deok Jun Kim, Hwan Jung Roh, Bang Hur, Kang Dae Lee, Spagnoli Spagnoli; Korean J Pathol. 2000;34(11):901-908.

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Abstract PDF: MAGE (melanoma antigen gene) is a tumor specific shared antigen, presented by HLA class I molecules, which is recognized by cytotoxic T lymphocytes. MAGE proteins are expressed in malignant tumor cells, in contrast to no expression in normal or benign tissues except for testis and placenta. MAGE might be a potential target for immunotherapy of malignant tumors. However, its biological aspects associated with cell cycle are not yet described. The flow cytometry is a useful tool for objective and quantitative analyses of heterogenous tumor cell population. To understand the status of MAGE related to cell cycle and its relationship with p53 as the G1 checkpoint regulator, p21, and PCNA as a proliferative index, we investigated expression of MAGE-3 protein, mutant p53, p21, and PCNA by flow cytometry and immunohistochemical stain. In addition, double stains for MAGE-3/p53, p53/PCNA, and p53/p21 were analysed with bivariate flow cytometry. DNA histograms using MAGE-3/PI (DNA) and p53/PI (DNA) were also analysed. The cell line (PNUH- 12) used for this study originated from a hypopharyngeal squamous cell carcinoma, which has point mutation (exon 7, C-->G) of p53. The expression rate of MAGE-3 was 83%, PCNA 85%, and p53 81%. No expression for p21 was identified. MAGE-3 was expressed in cytoplasm, while both PCNA and p53 were expressed in nuclei of tumor cells. With bivariate analyses, coexpression rates of MAGE-3/p53 and p53/PCNA were 0.96 and 0.97, respectively. Both MAGE-3 and p53 showed constantly high level throughout the cell cycle. These results suggest that expression of MAGE-3 and mutant p53 is not dependent on the cell cycle. p21 seems to be inactivated.

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