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Volume 53(4); July 2019
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Reviews
PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future
Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2019;53(4):199-206.   Published online May 2, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.24
Correction in: J Pathol Transl Med 2020;54(2):196
  • 11,288 View
  • 572 Download
  • 35 Citations
AbstractAbstract PDF
Blockade of the programmed cell death-1 (PD-1) axis has already been established as an effective treatment of non-small cell lung cancer. Immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) protein is the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer. Because each PD-1/PD-L1 blockade was approved together with a specific PD-L1 IHC assay used in the clinical trials, pathologists have been challenged with performing various assays with a limited sample. To provide a more unified understanding of this, several cross-validation studies between platforms have been performed and showed consistent results. However, the interchangeability of assays may be limited in practice because of the risk of misclassification of patients for the treatment. Furthermore, several issues, including the temporal and spatial heterogeneity of PD-L1 expression in the tumor, and the potential for cytology specimens to be used as an alternative to tissue samples for PD-L1 testing, have still not been resolved. In the future, one of the main aims of immunotherapy research should be to find a novel predictive biomarker for PD-1 blockade therapy and a way to combine it with PD-L1 IHC and other tests.
How to Foster Professional Values during Pathology Residency
Yong-Jin Kim
J Pathol Transl Med. 2019;53(4):207-209.   Published online June 27, 2019
DOI: https://doi.org/10.4132/jptm.2019.06.12
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AbstractAbstract PDF
The importance of professional and ethical behavior by physicians both in training and in practice cannot be overemphasized, particularly in pathology. Professionalism education begins in medical school, and professional attitudes and behaviors are further internalized during residency. Learning how to be a professional is a vital part of residency training. While hospital- or institution-based lecture style educational programs exist, they are often ineffective because the curriculum is not applicable to all specialties, although the basic concepts are the same. In this paper, the author suggests ways for institutions to develop professional attitude assessments and to survey residents’ responses to various unprofessional situations using case scenarios.
Current Status of and Perspectives on Cervical Cancer Screening in Korea
Sung-Chul Lim, Chong Woo Yoo
J Pathol Transl Med. 2019;53(4):210-216.   Published online May 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.11
  • 6,203 View
  • 214 Download
  • 6 Citations
AbstractAbstract PDF
Since the introduction of the Papanicolaou (Pap) smear system in 1943, cervicovaginal cytology has been used as a standard screening test for cervical cancer. The dissemination of this test contributed to reductions of the incidence and mortality of cervical cancer worldwide. In Korea, regular health check-ups for industrial workers and their family members were introduced in 1988 and were performed as part of the National Cancer Screening Program in 1999. As a result, the incidence of cervical cancer in Korea has been steadily decreasing. However, about 800 cases of cervical cancer-related deaths are reported each year due to false-negative test results. Hence, new screening methods have been proposed. Liquid-based cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap smears. Since then, other LBC methods have been developed and utilized, including the human papilloma virus test—a method with higher sensitivity that requires fewer screenings. In this study, we review current issues and future perspectives related to cervical cancer screening in Korea.
Original Articles
Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer
Ae Ri An, Kyoung Min Kim, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Yong Chul Lee, Jong Hun Kim, Han Jung Chae, Myoung Ja Chung
J Pathol Transl Med. 2019;53(4):217-224.   Published online March 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.20
  • 4,801 View
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  • 8 Citations
AbstractAbstract PDF
Background
Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC).
Methods
We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking.
Results
The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05).
Conclusions
The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.
CpG Island Methylation in Sessile Serrated Adenoma/Polyp of the Colorectum: Implications for Differential Diagnosis of Molecularly High-Risk Lesions among Non-dysplastic Sessile Serrated Adenomas/Polyps
Ji Ae Lee, Hye Eun Park, Seung-Yeon Yoo, Seorin Jeong, Nam-Yun Cho, Gyeong Hoon Kang, Jung Ho Kim
J Pathol Transl Med. 2019;53(4):225-235.   Published online March 19, 2019
DOI: https://doi.org/10.4132/jptm.2019.03.12
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  • 3 Citations
AbstractAbstract PDFSupplementary Material
Background
Although colorectal sessile serrated adenomas/polyps (SSA/Ps) with morphologic dysplasia are regarded as definite high-risk premalignant lesions, no reliable grading or risk-stratifying system exists for non-dysplastic SSA/Ps. The accumulation of CpG island methylation is a molecular hallmark of progression of SSA/Ps. Thus, we decided to classify non-dysplastic SSA/Ps into risk subgroups based on the extent of CpG island methylation.
Methods
The CpG island methylator phenotype (CIMP) status of 132 non-dysplastic SSA/Ps was determined using eight CIMP-specific promoter markers. SSA/Ps with CIMP-high and/or MLH1 promoter methylation were regarded as a high-risk subgroup.
Results
Based on the CIMP analysis results, methylation frequency of each CIMP marker suggested a sequential pattern of CpG island methylation during progression of SSA/P, indicating MLH1 as a late-methylated marker. Among the 132 non-dysplastic SSA/Ps, 34 (26%) were determined to be high-risk lesions (33 CIMP-high and 8 MLH1-methylated cases; seven cases overlapped). All 34 high-risk SSA/Ps were located exclusively in the proximal colon (100%, p = .001) and were significantly associated with older age (≥ 50 years, 100%; p = .003) and a larger histologically measured lesion size (> 5 mm, 100%; p = .004). In addition, the high-risk SSA/Ps were characterized by a relatively higher number of typical base-dilated serrated crypts.
Conclusions
Both CIMP-high and MLH1 methylation are late-step molecular events during progression of SSA/Ps and rarely occur in SSA/Ps of young patients. Comprehensive consideration of age (≥ 50), location (proximal colon), and histologic size (> 5 mm) may be important for the prediction of high-risk lesions among non-dysplastic SSA/Ps.
Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects
Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk
J Pathol Transl Med. 2019;53(4):236-243.   Published online April 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.03.21
  • 4,790 View
  • 111 Download
  • 3 Citations
AbstractAbstract PDF
Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.
Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer
So Young Kim, Kyung Un Choi, Chungsu Hwang, Hyung Jung Lee, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Jae Ho Kim, Ki Hyung Kim, Dong Soo Suh, Byung Su Kwon
J Pathol Transl Med. 2019;53(4):244-252.   Published online May 2, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.16
  • 4,739 View
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  • 2 Citations
AbstractAbstract PDF
Background
Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis.
Methods
Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy.
Results
CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001).
Conclusions
Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.
Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients
Hyo Jeong Kang, Soon Auck Hong, Seak Hee Oh, Kyung Mo Kim, Han-Wook Yoo, Gu-Hwan Kim, Eunsil Yu
J Pathol Transl Med. 2019;53(4):253-260.   Published online May 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.05.03
  • 4,853 View
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  • 4 Citations
AbstractAbstract PDF
Background
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea.
Methods
The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations.
Results
The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT.
Conclusions
PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.
Case Study
Primary Necrobiotic Xanthogranulomatous Sialadenitis with Submandibular Gland Localization without Skin Involvement
Myunghee Kang, Na Rae Kim, Dong Hae Chung, Jae Yeon Seok, Dong Young Kim
J Pathol Transl Med. 2019;53(4):261-265.   Published online January 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.01.08
  • 4,621 View
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  • 5 Citations
AbstractAbstract PDF
Necrobiotic xanthogranulomatous reaction is a multiorgan, non-Langerhans cell histiocytosis with an unknown etiology. Occurrence in the salivary gland is extremely rare. We recently identified a case of necrobiotic xanthogranulomatous sialadenitis in a 73-year-old Korean woman who presented with a painless palpable lesion in the chin. There was no accompanying cutaneous lesion. Partial resection and subsequent wide excision with neck dissection were performed. Pathological examination showed a severe inflammatory lesion that included foamy macrophages centrally admixed with neutrophils, eosinophils, lymphocytes, plasma cells, and scattered giant cells, as well as necrobiosis. During the 12-month postoperative period, no grossly remarkable change in size was noted. Necrobiotic xanthogranulomatous inflammation may be preceded by or combined with hematologic malignancy. Although rare, clinicians and radiologists should be aware that an adhesive necrobiotic xanthogranuloma in the salivary gland may present with a mass-like lesion. Further evaluation for hematologic disease and close follow-up are needed when a pathologic diagnosis is made.
Case Report
Rectal Invasion by Prostatic Adenocarcinoma That Was Initially Diagnosed in a Rectal Polyp on Colonoscopy
Ghilsuk Yoon, Man-Hoon Han, An Na Seo
J Pathol Transl Med. 2019;53(4):266-269.   Published online April 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.03.25
  • 4,643 View
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  • 4 Citations
AbstractAbstract PDF
Despite anatomical proximity, prostatic adenocarcinoma with rectal invasion is extremely rare. We present a case of rectal invasion by prostatic adenocarcinoma that was initially diagnosed from a rectal polyp biopsied on colonoscopy in a 69-year-old Korean man. He presented with dull anal pain and voiding discomfort for several days. Computed tomography revealed either prostatic adenocarcinoma with rectal invasion or rectal adenocarcinoma with prostatic invasion. His tumor marker profile showed normal prostate specific antigen (PSA) level and significantly elevated carcinoembryonic antigen level. Colonoscopy was performed, and a specimen was obtained from a round, 1.5 cm, sessile polyp that was 1.5 cm above the anal verge. Microscopically, glandular tumor structures infiltrated into the rectal mucosa and submucosa. Immunohistochemically, the tumor cells showed alpha-methylacyl-CoA-racemase positivity, PSA positivity, and caudal-related homeobox 2 negativity. The final diagnosis of the rectal polyp was consistent with prostatic adenocarcinoma. Here, we present a rare case that could have been misdiagnosed as rectal adenocarcinoma.
Brief Case Report
Endocervical Adenocarcinoma In Situ Phenotype with Ovarian Metastasis
Hyun-Soo Kim, Yeon Seung Chung, Moon Sik Kim, Hyang Joo Ryu, Ji Hee Lee
J Pathol Transl Med. 2019;53(4):270-272.   Published online December 28, 2018
DOI: https://doi.org/10.4132/jptm.2018.12.17
  • 4,232 View
  • 124 Download
  • 6 Citations
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JPTM : Journal of Pathology and Translational Medicine