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Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma.

Hyun Jung KIM ; Kyeongmee PARK ; Jung Yeon KIM ; Guhyun KANG ; Geumhee GWAK ; Inseok PARK

Journal of Pathology and Translational Medicine.2017;51(4):403-409. doi:10.4132/jptm.2017.03.18

BACKGROUND: Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. METHODS: A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). RESULTS: The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05). According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05). CONCLUSIONS: In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.
Adenocarcinoma, Mucinous* ; Breast Neoplasms ; Breast* ; Humans ; Lymph Nodes ; Mucins* ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Risk Factors

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HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient.

Dang Anh Thu PHAN ; Vu Thien NGUYEN ; Thi Ngoc Ha HUA ; Quoc Dat NGO ; Thi Phuong Thao DOAN ; Sao Trung NGUYEN ; Anh Tu THAI ; Van Thanh NGUYEN

Journal of Pathology and Translational Medicine.2017;51(4):396-402. doi:10.4132/jptm.2017.04.24

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. METHODS: We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated. RESULTS: In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+. CONCLUSIONS: HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.
Asian Continental Ancestry Group* ; Fluorescence ; Gene Amplification ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Population Characteristics* ; Receptor, Epidermal Growth Factor ; Stomach Neoplasms ; Trastuzumab

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Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients.

Sung Joo KIM ; Soyeon AN ; Jae Hoon LEE ; Joo Young KIM ; Ki Byung SONG ; Dae Wook HWANG ; Song Cheol KIM ; Eunsil YU ; Seung Mo HONG

Journal of Pathology and Translational Medicine.2017;51(4):388-395. doi:10.4132/jptm.2017.03.19

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.
Carcinogenesis* ; Classification ; Disease-Free Survival ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreas ; Pancreatic Neoplasms ; Progesterone* ; Prognosis ; Receptors, Progesterone* ; Survival Rate ; Telomere ; World Health Organization

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Morphological Features and Immunohistochemical Expression of p57Kip2 in Early Molar Pregnancies and Their Relations to the Progression to Persistent Trophoblastic Disease.

Marwa KHASHABA ; Mohammad ARAFA ; Eman ELSALKH ; Reda HEMIDA ; Wagiha KANDIL

Journal of Pathology and Translational Medicine.2017;51(4):381-387. doi:10.4132/jptm.2017.04.28

BACKGROUND: Although the morphological features characteristic of products of conception specimens including molar pregnancies are well described, substantial histopathological similarities are observed between the different entities, especially in cases of early pregnancies. Furthermore, there are no current solid criteria that could predict cases with progression to persistent gestational trophoblastic disease. In this study, we aimed to determine the most specific histopathological and immunohistochemical features required for accurate diagnosis that can reliably predict the clinical behavior. METHODS: Sixty-five cases of products of conception were reviewed clinically and pathologically, and any progression to persistent gestational trophoblastic disease (GTD), if present, was noted. Pathological assessment of the archival material included re-cut sections of 5 μm in thickness, routine staining with hematoxylin and eosin and immunohistochemical staining of p57Kip2. RESULTS: Certain histopathological criteria were found to be significant in differentiation between complete hydatidiform mole (CHM) and partial hydatidiform mole including villous shape and outline, villous trophoblast hyperplasia, and atypia in extravillous trophoblasts. There were no significant differences in any morphological or immunohistochemical features between cases with or without subsequent development of GTD. CONCLUSIONS: Histopathological diagnosis of molar pregnancy remains problematic especially in early gestation. Their diagnosis should be stated after a constellation of specific histopathological criteria in order not to miss CHM. p57Kip2 immunohistochemistry is of great value in diagnosis of cases that had equivocal morphology by histopathological examination. However, there were no significant features to predict cases that subsequently developed persistent GTD.
Diagnosis ; Eosine Yellowish-(YS) ; Female ; Fertilization ; Gestational Trophoblastic Disease ; Hematoxylin ; Hydatidiform Mole* ; Hyperplasia ; Immunohistochemistry ; Molar* ; Pregnancy ; Trophoblasts*

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Basaloid Squamous Cell Carcinoma of the Head and Neck: Subclassification into Basal, Ductal, and Mixed Subtypes Based on Comparison of Clinico-pathologic Features and Expression of p53, Cyclin D1, Epidermal Growth Factor Receptor, p16, and Human Papilloma.

Kyung Ja CHO ; Se Un JEONG ; Sung Bae KIM ; Sang wook LEE ; Seung Ho CHOI ; Soon Yuhl NAM ; Sang Yoon KIM

Journal of Pathology and Translational Medicine.2017;51(4):374-380. doi:10.4132/jptm.2017.03.03

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma with distinct pathologic characteristics. The histogenesis of BSCC is not fully understood, and the cancer has been suggested to originate from a totipotent primitive cell in the basal cell layer of the surface epithelium or in the proximal duct of secretory glands. METHODS: Twenty-six cases of head and neck BSCC from Asan Medical Center, Seoul, Korea, reported during a 14-year-period were subclassified into basal, ductal, and mixed subtypes according to the expression of basal (cytokeratin [CK] 5/6, p63) or ductal markers (CK7, CK8/18). The cases were also subject to immunohistochemical study for CK19, p53, cyclin D1, epidermal growth factor receptor (EGFR), and p16 and to in situ hybridization for human papillomavirus (HPV), and the results were clinico-pathologically compared. RESULTS: Mixed subtype (12 cases) was the most common, and these cases showed hypopharyngeal predilection, older age, and higher expression of CK19, p53, and EGFR than other subtypes. The basal subtype (nine cases) showed frequent comedo-necrosis and high expression of cyclin D1. The ductal subtype (five cases) showed the lowest expression of p53, cyclin D1, and EGFR. A small number of p16- and/or HPV-positive cases were not restricted to one subtype. BSCC was the cause of death in 19 patients, and the average follow-up period for all patients was 79.5 months. Overall survival among the three subtypes was not significantly different. CONCLUSIONS: The results of this study suggest a heterogeneous pathogenesis of head and neck BSCC. Each subtype showed variable histology and immunoprofiles, although the clinical implication of heterogeneity was not determined in this study.
Carcinoma, Squamous Cell* ; Cause of Death ; Chungcheongnam-do ; Cyclin D1* ; Cyclins* ; Epidermal Growth Factor* ; Epithelial Cells* ; Epithelium ; Follow-Up Studies ; Head* ; Humans* ; In Situ Hybridization ; Korea ; Neck* ; Population Characteristics ; Receptor, Epidermal Growth Factor* ; Seoul ; Tumor Suppressor Protein p53

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Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma.

Myung Giun NOH ; Sung Sun KIM ; Eu Chang HWANG ; Dong Deuk KWON ; Chan CHOI

Journal of Pathology and Translational Medicine.2017;51(4):365-373. doi:10.4132/jptm.2017.05.04

BACKGROUND: Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. METHODS: The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. RESULTS: YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. CONCLUSIONS: The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.
Adenocarcinoma* ; Breast ; Carcinogenesis ; Cell Proliferation ; Colon ; Cytoplasm ; Epithelial Cells ; Humans ; Immunohistochemistry ; Liver ; Lung ; Ovarian Neoplasms ; Prognosis ; Proportional Hazards Models ; Prostate* ; Prostate-Specific Antigen ; Recurrence ; Skin ; Stem Cells ; Tumor Burden

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Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma.

Cheol LEE ; Bohyun KIM ; Boram SONG ; Kyung Chul MOON

Journal of Pathology and Translational Medicine.2017;51(4):359-364. doi:10.4132/jptm.2017.03.16

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry. METHODS: We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed. RESULTS: Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage. CONCLUSIONS: Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.
Adipogenesis ; Carcinoma, Renal Cell* ; Colonic Neoplasms ; Disease-Free Survival ; Epigenomics ; Fingers ; Histones ; Humans ; Immunohistochemistry ; Multivariate Analysis ; Nephrectomy ; Plants ; Prognosis ; Seoul ; Stomach Neoplasms

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Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification.

Hyun Jung KIM ; Young Hyeh KO ; Ji Eun KIM ; Seung Sook LEE ; Hyekyung LEE ; Gyeongsin PARK ; Jin Ho PAIK ; Hee Jeong CHA ; Yoo Duk CHOI ; Jae Ho HAN ; Jooryung HUH

Journal of Pathology and Translational Medicine.2017;51(4):352-358. doi:10.4132/jptm.2017.03.15

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.
B-Lymphocytes ; Burkitt Lymphoma ; Classification* ; Diagnosis ; Herpesvirus 4, Human ; Humans ; Lymphoma ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Peripheral ; Lymphoproliferative Disorders* ; T-Lymphocytes ; World Health Organization

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Rare Gastric Lesions Associated with Helicobacter pylori Infection: A Histopathological Review.

Mee JOO

Journal of Pathology and Translational Medicine.2017;51(4):341-351. doi:10.4132/jptm.2017.04.03

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. However, some rare gastric lesions exhibiting distinctive histological features may also be associated with H. pylori infection, including lymphocytic gastritis, granulomatous gastritis, Russell body gastritis, or crystal-storing histiocytosis. Although diverse factors can contribute to their development, there is convincing evidence that H. pylori infection may play a pathogenic role. These findings are mainly based on studies in patients with these lesions who exhibited clinical and histological improvements after H. pylori eradication therapy. Thus, H. pylori eradication therapy might be indicated in patients with no other underlying disease, particularly in countries with a high prevalence of H. pylori infection. This review describes the characteristic histological features of these rare lesions and evaluates the evidence regarding a causative role for H. pylori infection in their pathogenesis.
Adenocarcinoma ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Histiocytosis ; Humans ; Immunoglobulins ; Lymphoma, B-Cell, Marginal Zone ; Peptic Ulcer ; Prevalence ; Stomach ; Stomach Diseases

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Mucosal Schwann Cell Hamartoma in Colorectal Mucosa: A Rare Benign Lesion That Resembles Gastrointestinal Neuroma.

Jiheun HAN ; Yosep CHONG ; Tae Jung KIM ; Eun Jung LEE ; Chang Suk KANG

Journal of Pathology and Translational Medicine.2017;51(2):187-189. doi:10.4132/jptm.2016.07.02

No abstract available.

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