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Volume 50(4); July 2016
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Original Articles
Aquaporin 1 Is an Independent Marker of Poor Prognosis in Lung Adenocarcinoma
Sumi Yun, Ping-Li Sun, Yan Jin, Hyojin Kim, Eunhyang Park, Soo Young Park, Kyuho Lee, Kyoungyul Lee, Jin-Haeng Chung
J Pathol Transl Med. 2016;50(4):251-257.   Published online June 7, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.30
  • 8,118 View
  • 111 Download
  • 16 Citations
AbstractAbstract PDF
Background
Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers.
Methods
We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray.
Results
AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression- free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031).
Conclusions
AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.
Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases
Soomin Ahn, Soo Hyun Hwang, Joungho Han, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn, Woong-Yang Park
J Pathol Transl Med. 2016;50(4):258-263.   Published online May 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.04.19
  • 9,397 View
  • 219 Download
  • 30 Citations
AbstractAbstract PDF
Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors.
Methods
We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples.
Results
Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment.
Conclusions
NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.
Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas
Inju Cho, Mija Lee, Sharon Lim, Ran Hong
J Pathol Transl Med. 2016;50(4):264-269.   Published online June 23, 2016
DOI: https://doi.org/10.4132/jptm.2016.04.24
  • 7,576 View
  • 54 Download
  • 1 Citations
AbstractAbstract PDF
Background
Parafibromin is a product of the tumor suppressor gene that has been studied as a potential indicator of tumor aggressiveness in the parathyroid, breast, colorectum, and stomach. However, the clinical significance and potential function of parafibromin expression in head and neck squamous cell carcinomas remain largely unknown. The aim of this study was to evaluate the expression of parafibromin in laryngeal squamous cell carcinoma (LSCC) and to verify its potential as a biomarker of tumor behavior.
Methods
Parafibromin expression was evaluated in 30 cases of LSCC using immunohistochemistry. The correlations between parafibromin expression and clinicopathologic parameters were investigated.
Results
Parafibromin expression was positive in 15 cases (50%) and negative in 15 cases (50%). Tumor size and T stage showed a statistically significant inverse relationship with parafibromin expression (p=.028 and p<.001, respectively). Parafibromin expression was not associated with age, sex, lymph node metastasis, tumor differentiation, or tumor location. There was no statistically significant relationship between parafibromin expression and progression-free survival in the patients (p>.05).
Conclusions
Our results indicate that the downregulation or loss of parafibromin expression can be employed as a novel marker of tumor progression or aggressiveness in LSCC.
Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases
Kyu Sang Lee, Soo Kyung Nam, Jiwon Koh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
J Pathol Transl Med. 2016;50(4):270-277.   Published online May 31, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.19
  • 7,319 View
  • 90 Download
  • 14 Citations
AbstractAbstract PDF
Background
The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
Methods
miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
Results
The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
Conclusions
miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.
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
  • 8,611 View
  • 102 Download
  • 19 Citations
AbstractAbstract 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.
Morphometric Analysis of Thyroid Follicular Cells with Atypia of Undetermined Significance
Youngjin Kang, Yoo Jin Lee, Jiyoon Jung, Youngseok Lee, Nam Hee Won, Yang Seok Chae
J Pathol Transl Med. 2016;50(4):287-293.   Published online June 13, 2016
DOI: https://doi.org/10.4132/jptm.2016.04.04
  • 8,056 View
  • 84 Download
  • 1 Citations
AbstractAbstract PDF
Background
Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions.
Methods
We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups.
Results
The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different.
Conclusions
We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.
Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients
Min-Kyung Yeo, Ahwon Lee, Soo Young Hur, Jong Sup Park
J Pathol Transl Med. 2016;50(4):294-299.   Published online June 26, 2016
DOI: https://doi.org/10.4132/jptm.2016.05.09
  • 6,913 View
  • 75 Download
  • 2 Citations
AbstractAbstract PDF
Background
Human papillomavirus (HPV) is a major risk factor for cervical cancer.
Methods
We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients.
Results
The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group.
Conclusions
The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.
Case Study
Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease
Seokhwi Kim, Hyunsik Bae, Misun Choi, Binnari Kim, Jin Seok Heo, Ho Seong Kim, Seung Hee Choi, Kee-Taek Jang
J Pathol Transl Med. 2016;50(4):300-305.   Published online January 11, 2016
DOI: https://doi.org/10.4132/jptm.2015.12.01
  • 7,865 View
  • 84 Download
  • 3 Citations
AbstractAbstract PDF
IgG4-related disease (IgG4-RD) may involve multiple organs. Although it usually presents as diffuse organ involvement, localized mass-forming lesions have been occasionally encountered in pancreas. However, the same pattern has been seldom reported in biliary tract. A 61-year-old male showed a hilar bile duct mass with multiple enlarged lymph nodes in imaging studies and he underwent trisectionectomy under impression of cholangiocarcinoma. Gross examination revealed a mass-like lesion around hilar bile duct. Histopathologically, dense lymphoplasmacytic infiltration and storiform fibrosis were identified without evidence of malignancy. Immunohistochemical stain demonstrated rich IgG4-positive plasma cell infiltration. Follow-up imaging studies disclosed multiple enlarged lymph nodes with involvement of pancreas and perisplenic soft tissue. The lesions have been significantly reduced after steroid treatment, which suggests multi-organ involvement of systemic IgG4-RD. Here, we report an unusual localized mass-forming IgG4-related cholangitis as an initial presentation of IgG4-RD, which was biliary manifestation of systemic IgG4-related autoimmune disease.
Brief Case Reports
Intramuscular Tenosynovial Giant Cell Tumor, Diffuse-Type
Yoo Jin Lee, Youngjin Kang, Jiyoon Jung, Seojin Kim, Chul Hwan Kim
J Pathol Transl Med. 2016;50(4):306-308.   Published online January 11, 2016
DOI: https://doi.org/10.4132/jptm.2015.11.15
  • 7,144 View
  • 98 Download
  • 4 Citations
PDF
IgG4-Related Sclerosing Mesenteritis
Seok Joo Lee, Cheol Keun Park, Woo Ick Yang, Sang Kyum Kim
J Pathol Transl Med. 2016;50(4):309-311.   Published online January 11, 2016
DOI: https://doi.org/10.4132/jptm.2015.12.03
  • 8,621 View
  • 137 Download
  • 14 Citations
PDF
Carney Complex with Multiple Cardiac Myxomas, Pigmented Nodular Adrenocortical Hyperplasia, Epithelioid Blue Nevus, and Multiple Calcified Lesions of the Testis: A Case Report
Hyunchul Kim, Hyun-Yee Cho, Jeong Nam Lee, Kook-Yang Park
J Pathol Transl Med. 2016;50(4):312-314.   Published online February 4, 2016
DOI: https://doi.org/10.4132/jptm.2015.11.12
  • 6,641 View
  • 63 Download
  • 3 Citations
PDF
Tailgut Cyst in a Neonate: A Case Report
Ji Hyen Lee, Yun Suk Lee, So Yeon Shim, Su Jin Cho, Eun Ae Park, Soon Sup Chung, Sanghui Park
J Pathol Transl Med. 2016;50(4):315-317.   Published online April 6, 2016
DOI: https://doi.org/10.4132/jptm.2015.11.27
  • 7,222 View
  • 73 Download
  • 2 Citations
PDF
Gastric Mixed Adenoneuroendocrine Carcinoma with Squamous Differentiation: A Case Report
Han-Ik Bae, Chaeyoon Lee, Young-Min Jo, Ohkyung Kwon, Wansik Yu, Mee-Seon Kim, An Na Seo
J Pathol Transl Med. 2016;50(4):318-321.   Published online January 11, 2016
DOI: https://doi.org/10.4132/jptm.2015.10.17
  • 6,444 View
  • 61 Download
  • 2 Citations
PDF
Primary Cutaneous Adenoid Cystic Carcinoma Arising in Umbilicus
Seok Joo Lee, Woo Ick Yang, Sang Kyum Kim
J Pathol Transl Med. 2016;50(4):322-324.   Published online January 11, 2016
DOI: https://doi.org/10.4132/jptm.2015.11.24
  • 6,620 View
  • 83 Download
  • 4 Citations
PDF
Retraction
Notice of Retraction: Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats
Jae Chul Lee, Choong Ik Cha, Dong-Sik Kim, Soo Young Choe
J Pathol Transl Med. 2016;50(4):325-325.   Published online July 15, 2016
DOI: https://doi.org/10.4132/jptm.2015.09.11.r
Retracts: J Pathol Transl Med 2015;49(6):472
  • 6,306 View
  • 88 Download
  • 1 Citations
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JPTM : Journal of Pathology and Translational Medicine