Journal of Pathology and Translational Medicine

Original Articles

Analysis of PAX8 immunohistochemistry in lung cancers: a meta-analysis: Jae Han Jeong, Nae Yu Kim, Jung-Soo Pyo; J Pathol Transl Med. 2020;54(4):300-309. Published online July 10, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.08

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Background
In this meta-analysis, we aimed to evaluate the PAX8 immunohistochemical expressions in primary lung cancers and metastatic cancers to the lung.
Methods
We identified and reviewed relevant articles from the PubMed databases. Ultimately, 18 articles were included in this meta-analysis. PAX8 expression rates were analyzed and compared between primary and metastatic lung cancers.
Results
The PAX8 expression rate in primary lung cancers was 0.042 (95% confidence interval [CI], 0.025 to 0.071). PAX8 expression rates of small cell (0.129; 95% CI, 0.022 to 0.496) and non-small cell carcinomas of the lung (0.037; 95% CI, 0.022 to 0.061) were significantly different (p=.049 in a meta-regression test). However, the PAX8 expression rates of adenocarcinoma (0.013; 95% CI, 0.006 to 0.031) and squamous cell carcinoma (0.040; 95% CI, 0.016 to 0.097) were not significantly different. PAX8 expression rates of metastatic carcinomas to the lung varied, ranging from 1.8% to 94.9%. Metastatic carcinomas from the lung to other organs had a PAX8 expression rate of 6.3%. The PAX8 expression rates of metastatic carcinomas from the female genital organs, kidneys, and thyroid gland to the lung were higher than those of other metastatic carcinomas.
Conclusions
Primary lung cancers had a low PAX8 expression rate regardless of tumor subtype. However, the PAX8 expression rates of metastatic carcinomas from the female genital organs, kidneys, and thyroid were significantly higher than those of primary lung cancers.

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Sakurako Harada‐Kagitani, Yusuke Kouchi, Yoshiki Shinomiya, Takuto Hiramoto, Tomoyuki Arai, Toyoyuki Hanazawa, Kiyotaka Onodera, Kaito Nakama, Takanori Aihara, Masayuki Ota, Jun‐Ichiro Ikeda, Takashi Kishimoto
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Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component
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Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis: Jung-Soo Pyo, Nae Yu Kim, Won Jin Cho; J Pathol Transl Med. 2019;53(3):173-179. Published online March 5, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.03

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Abstract PDF

Background
Although the correlation between low claudin-1 expression and worse prognosis has been reported, details on the prognostic implications of claudin-1 expression in various malignant tumors remain unclear. The present study aimed to elucidate the prognostic roles of claudin- 1 immunohistochemistry (IHC) in various malignant tumors through a meta-analysis.
Methods
The study included 2,792 patients from 22 eligible studies for assessment of the correlation between claudin-1 expression and survival rate in various malignant tumors. A subgroup analysis based on the specific tumor and evaluation criteria of claudin-1 IHC was conducted.
Results
Low claudin-1 expression was significantly correlated with worse overall survival (OS) (hazard ratio [HR], 1.851; 95% confidence interval [CI], 1.506 to 2.274) and disease-free survival (DFS) (HR, 2.028; 95% CI, 1.313 to 3.134) compared to high claudin-1 expression. Breast, colorectal, esophageal, gallbladder, head and neck, and lung cancers, but not cervical, liver or stomach cancers, were significantly correlated with worse OS. Breast, colorectal, esophageal, and thyroid cancers with low claudin-1 expression were associated with poorer DFS. In the lower cut-off subgroup (< 25.0%) with respect to claudin-1 IHC, low claudin-1 expression was significantly correlated with worse OS and DFS.
Conclusions
Taken together, low claudin-1 IHC expression is significantly correlated with worse survival in various malignant tumors. More detailed criteria for claudin-1 IHC expression in various malignant tumors are needed for application in daily practice.

Citations

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Expression and Targeted Application of Claudins Family in Hepatobiliary and Pancreatic Diseases
Fangqian Du, Yuwei Xie, Shengze Wu, Mengling Ji, Bingzi Dong, Chengzhan Zhu
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The Significance of Relative Claudin Expression in Odontogenic Tumors
Ekarat Phattarataratip, Kraisorn Sappayatosok
Head and Neck Pathology.2020; 14(2): 480. CrossRef
Claudin-1 upregulation is associated with favorable tumor features and a reduced risk for biochemical recurrence in ERG-positive prostate cancer
Simon Kind, Franziska Büscheck, Doris Höflmayer, Claudia Hube-Magg, Martina Kluth, Maria Christina Tsourlakis, Stefan Steurer, Till S. Clauditz, Andreas M. Luebke, Eike Burandt, Waldemar Wilczak, Andrea Hinsch, David Dum, Sören Weidemann, Christoph Fraune
World Journal of Urology.2020; 38(9): 2185. CrossRef
Characterisation of endogenous Claudin‐1 expression, motility and susceptibility to hepatitis C virus in CRISPR knock‐in cells
Camille M.H. Clément, Maika S. Deffieu, Cristina M. Dorobantu, Thomas F. Baumert, Nilda Vanesa Ayala‐Nunez, Yves Mély, Philippe Ronde, Raphael Gaudin
Biology of the Cell.2020; 112(5): 140. CrossRef
Comment on “Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis”
Bolin Wang, Yan Huang
Journal of Pathology and Translational Medicine.2019; 53(6): 411. CrossRef

Prognostic Role of Metastatic Lymph Node Ratio in Papillary Thyroid Carcinoma: Jung-Soo Pyo, Jin Hee Sohn, Kyungseek Chang; J Pathol Transl Med. 2018;52(5):331-338. Published online August 30, 2018; DOI: https://doi.org/10.4132/jptm.2018.08.07

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Abstract PDF

Background
The aim of this study is to elucidate the clinicopathological significances, including the prognostic role, of metastatic lymph node ratio (mLNR) and tumor deposit diameter in papillary thyroid carcinoma (PTC) through a retrospective review and meta-analysis.
Methods
We categorized the cases into high (≥ 0.44) and low mLNR (< 0.44) and investigated the correlations with clinicopathological parameters in 64 PTCs with neck level VI lymph node (LN) metastasis. In addition, meta-analysis of seven eligible studies was used to investigate the correlation between mLNR and survival.
Results
Among 64 PTCs with neck level VI LN metastasis, high mLNR was found in 34 PTCs (53.1%). High mLNR was significantly correlated with macrometastasis (tumor deposit diameter ≥ 0.2 cm), extracapsular spread, and number of metastatic LNs. Based on linear regression test, mLNR was significantly increased by the largest LN size but not the largest metastatic LN (mLN) size. High mLNR was not correlated with nuclear factor κB or cyclin D1 immunohistochemical expression, Ki-67 labeling index, or other pathological parameters of primary tumor. Based on meta-analysis, high mLNR significantly correlated with worse disease-free survival at the 5-year and 10-year follow-up (hazard ratio [HR], 4.866; 95% confidence interval [CI], 3.527 to 6.714 and HR, 5.769; 95% CI, 2.951 to 11.275, respectively).
Conclusions
Our data showed that high mLNR significantly correlated with worse survival, macrometastasis, and extracapsular spread of mLNs. Further cumulative studies for more detailed criteria of mLNR are needed before application in daily practice.

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Review

Thyroid Cytology in India: Contemporary Review and Meta-analysis: Shipra Agarwal, Deepali Jain; J Pathol Transl Med. 2017;51(6):533-547. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.04

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Abstract PDF

Fine-needle aspiration cytology (FNAC) is a screening test for triaging thyroid nodules, aiding in subsequent clinical management. However, the advantages have been overshadowed by the multiplicity of reporting systems and a wide range of nomenclature used. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formulated in 2007, to give the world a uniform thyroid cytology reporting system, facilitating easy interpretation by the clinicians. Here, we review the status of thyroid FNAC in India in terms of various reporting systems used including a meta-analysis of the previously published data. An extensive literature search was performed using internet search engines. The reports with detailed classification system used in thyroid cytology were included. The meta-analysis of published data was compared with the implied risk of malignancy by TBSRTC. More than 50 studies were retrieved and evaluated. TBSRTC is currently the most widely used reporting system with different studies showing good efficacy and interobserver concordance. Ancillary techniques have, as of now, limited applicability and acceptability in thyroid cytology in India. Twenty-eight published articles met the criteria for inclusion in the meta-analysis. When compared with TBSRTC recommendations, the meta-analysis showed a higher risk of malignancy for categories I and III. Thyroid FNAC is practiced all over India. TBSRTC has found widespread acceptance, with most institutions using this system for routine thyroid cytology reporting. However, reasons for a high malignancy risk for categories I and III need to be looked into. Various possible contributing factors are discussed in the review.

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Original Articles

Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer: Jinhyuk Choi, Chungyeul Kim, Hye Seung Lee, Yoo Jin Choi, Ha Yeon Kim, Jinhwan Lee, Hyeyoon Chang, Aeree Kim; J Pathol Transl Med. 2016;50(6):442-450. Published online October 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.08

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Abstract PDF

Background
Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast.
Methods
Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers.
Results
The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I² = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity.
Conclusions
These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.

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Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis: Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang; J Pathol Transl Med. 2016;50(4):278-286. Published online June 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.29

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Abstract PDF

Background
The clinicopathological characteristics and conclusive treatment modality for multifocal papillary thyroid microcarcinoma (mPTMC) have not been fully established.
Methods
A retrospective study, systematic review, and meta-analysis were conducted to elucidate the clinicopathological significance of mPTMC. We investigated the multiplicity of 383 classical papillary thyroid microcarcinomas (PTMCs) and the clinicopathological significance of incidental mPTMCs. Correlation between tumor recurrence and multifocality in PTMCs was evaluated through a systematic review and meta-analysis.
Results
Tumor multifocality was identified in 103 of 383 PTMCs (26.9%). On linear regression analysis, primary tumor diameter was significantly correlated with tumor number (R²=0.014, p=.021) and supplemental tumor diameter (R²=0.117, p=.023). Of 103 mPTMCs, 61 (59.2%) were non-incidental, with tumor detected on preoperative ultrasonography, and 42 (40.8%) were diagnosed (incidental mPTMCs) on pathological examination. Lymph node metastasis and higher tumor stage were significantly correlated with tumor multifocality. However, there was no difference in nodal metastasis or tumor stage between incidental and non-incidental mPTMCs. On meta-analysis, tumor multifocality was significantly correlated with tumor recurrence in PTMCs (odds ratio, 2.002; 95% confidence interval, 1.475 to 2.719, p<.001).
Conclusions
Our results show that tumor multifocality in PTMC, regardless of manner of detection, is significantly correlated with aggressive tumor behavior.

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MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis: Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang, Dong-Hoon Kim, Kyungeun Kim, In-Gu Do, Dong Hyun Kim; J Pathol Transl Med. 2015;49(3):249-256. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.03.27

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Background
While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinico-pathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). Methods: The present study investigated the correlation between MUC2 expression and clinico-pathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

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