Journal of Pathology and Translational Medicine

Original Articles

PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors: Yooju Shin, Jiyeon Hyeon, Boram Lee, Sang Yun Ha, Min Eui Hong, In Gu Do, Kyoung-Mee Kim; J Pathol Transl Med. 2015;49(1):23-29. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.08

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Background
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

Citations

Citations to this article as recorded by

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms
Gaoxiu Qi, Jinmeng Liu, Shuqi Tao, Wenyuan Fan, Haoning Zheng, Meihong Wang, Hanchao Yang, Yongting Liu, Huancai Liu, Fenghua Zhou
PeerJ.2023; 11: e15675. CrossRef
Loss of Slfn3 induces a sex-dependent repair vulnerability after 50% bowel resection
Emilie E. Vomhof-DeKrey, Jack T. Lansing, Diane C. Darland, Josey Umthun, Allie D. Stover, Christopher Brown, Marc D. Basson
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(2): G136. CrossRef
Phosphohistone H3 (PHH3) as a surrogate of mitotic figure count for grading in meningiomas: a comparison of PHH3 (S10) versus PHH3 (S28) antibodies
Napaporn Puripat, Kongsak Loharamtaweethong
Virchows Archiv.2019; 474(1): 87. CrossRef
Gastrointestinal Stromal Tumors Risk Stratification Utilizing Phospho-Histone H3 Evaluated by Manual Counting and Computer-Assisted Image Analysis
Cao Jin, Yan Huang, Mansoor Nasim, Yihe Yang, Lili Lee
International Journal of Surgical Pathology.2019; 27(7): 706. CrossRef
The utility of phosphohistone H3 in early prediction of benign and borderline phyllodes tumor recurrence
AymenM El-Saka, MohamedA Mlees, YomnaA Zamzam
Egyptian Journal of Pathology.2019; 39(2): 402. CrossRef
Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors
Min Jeong Kim, Mi Jung Kwon, Ho Suk Kang, Kyung Chan Choi, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hyoung-Chul Park
BioMed Research International.2018; 2018: 1. CrossRef
Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors
Piotr Lewitowicz, Jaroslaw Matykiewicz, Magdalena Chrapek, Dorota Koziel, Agata Horecka-Lewitowicz, Martyna Gluszek-Osuch, Iwona Wawrzycka, Stanisław Gluszek
Scanning.2018; 2018: 1. CrossRef
The mitosis‐specific marker phosphohistone‐H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome‐based study
Kin‐Long Chow, Ka‐Yu Tse, Ching‐Lung Cheung, Ka‐Wing Wong, Annie N Y Cheung, Richard W C Wong, Alice N H Chan, Nancy W F Yuen, Hextan Y S Ngan, Philip P C Ip
Histopathology.2017; 70(5): 746. CrossRef

Comparison of Liqui-PREP(TM) and Conventional Preparations in Thyroid Fine Needle Aspiration.: Eun Su Park, Eun Yoon Cho, In Gu Do, Soon Jae Kim, Jung Hee Shin, Boo Kyung Han, Young Lyun Oh; Korean J Pathol. 2009;43(6):550-556.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.550

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Abstract PDF

BACKGROUND
Liqui-PREP(TM) (LP) is a new liquid-based cytologic preparation that produces a thin layer of cells.
METHODS
Thyroid aspirates were obtained from 189 patients and divided to prepare pairs of conventional preparation (CP) and LP slides. The CP slides were routinely diagnosed by attending staffs and classified into the six categories. LP slides were independently evaluated by three cytopathologists and classified in an identical manner. Agreements between CP and LP diagnoses were investigated and interobserver variability of thyroid aspiration cytology results obtained using the LP method was determined using kappa values. RESULTS: CP and LP slides from 155 patients (83%) were identically classified by all of three cytopathologists. Concurrences between CP and LP diagnoses for the three cytopathologists were 89% (kappa=0.78), 92% (kappa=0.87), and 85% (kappa=0.70), respectively. Interobserver agreement among the three cytopathologists for LP slides ranged from substantial to almost perfect (kappa=0.84, 0.74 and 0.84). However, a lack of interobserver agreement was found for LP slides of the undetermined category as determined by original CP-based diagnoses. Moreover, cytomorphological alterations in the benign category appeared more worrisome for LP slides.
CONCLUSIONS
An awareness of the novel cytomorphologic changes induced by the LP method is needed to avoid misinterpretations.

Citations

Citations to this article as recorded by

Liquid base cytology in evaluation of thyroid nodules
Elahe Keyhani, Sasan A Sharghi, Rana Amini, Sina A Sharghi, Masoud Karimlou, Fatemeh A Moghaddam, Bagher Larijani
Journal of Diabetes & Metabolic Disorders.2014;[Epub] CrossRef
Diagnostic value of liquid‐based (Liqui‐PREP) preparations and interobserver reproducibility in fine needle aspiration cytology of the nodular thyroid lesions
U. S. Tetikkurt, F. Oz Puyan, F. Oz, N. Erdogan, S. Ceylan, A. Yakupoglu
Diagnostic Cytopathology.2012; 40(5): 388. CrossRef
Application of Bethesda System for Reporting Thyroid Aspiration Cytology
Kyungji Lee, Chan-Kwon Jung, Kyo-Young Lee, Ja-Seong Bae, Dong-Jun Lim, So-Lyung Jung
The Korean Journal of Pathology.2010; 44(5): 521. CrossRef

Case Reports

Gastrointestinal Stromal Tumor of the Colon Mimicking Inflammatory Fibroid Polyp with a Novel 63 bp c-kit Deletion Mutation: A Case Report.: In Gu Do, Cheol Keun Park, Sung Hyun Yoon, John Goldblum, Kyoung Mee Kim; Korean J Pathol. 2009;43(4):374-377.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.374

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Abstract PDF: Colonic gastrointestinal stromal tumors (GISTs) are rare and behave aggressively compared to GISTs in other parts of the gastrointestinal tract. Therefore, accurate diagnosis of GISTs and their distinction from other mesenchymal tumors is important for proper patient management and follow-up. Herein, we present an unusual case of a colonic GIST mimicking an inflammatory fibroid polyp with a novel 63 bp deletion mutation in exon 11 of the c-kit gene, which has not previously been reported. The tumor consisted of loosely arranged spindle cells and many inflammatory cells scattered throughout the tumor. Immunohistochemically, the tumor cells were focally and weakly positive for c-kit and diffusely positive for CD34, but were negative for PKC-theta, SMA, S-100 protein, ALK-1, and desmin. Our case re-emphasizes the broad morphologic spectrum of GISTs.

Fine Needle Aspiration Cytology of the Intraductal Papillary Mucinous Tumor of the Pancreas: A Case Report.: In Gu Do, Jae Hoon Park, Youn Wha Kim, Ju Hie Lee, Moon Ho Yang, Sung Wha Hong, Yong Koo Park; Korean J Cytopathol. 2003;14(2):91-95.

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Abstract PDF: Intraductal papillary mucinous tumor of the pancreas is characterized by intraductal papillary proliferation of mucin-producing epithelial cells with or without excessive mucin secretion. According to the degree of epithelial dysplasia, intraductal papillary mucinous tumor is classified into adenoma, borderline tumor, and carcinoma. We recently experienced a case of fine needle aspiration cytology of the intraductal papillary mucinous adenoma in a 69-year-old male. The fine needle aspiration cytology yielded flat sheets of columnar, mucin containing epithelial cells in the background of dense mucin containing degenerated cellular material and histiocytes.

Solitary Pulmonary Mixed Squamous Cell and Glandular Papilloma: A Brief Case Report.: Chan Ohk Sung, Jhingook Kim, In Gu Do, Joungho Han; Korean J Pathol. 2008;42(6):393-395.

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Abstract: Pulmonary mixed squamous cell and glandular papillomas are extremely rare-only a few cases have been reported worldwide. We report a case of mixed squamous cell and glandular papilloma that presented as a solitary pulmonary nodule in a 53-year-old man. The tumor was located in the peripheral small bronchus of the posterobasal segment of the right lower lobe. Microscopically, the tumor was composed of papillary structures lined by squamous and glandular epithelium with mucous material. The fibrovascular cores showed lymphoplasmacytic infiltrates.

Original Articles

Correlation Between Cyclooxygenase-2 Expression and HuR Cytoplasmic Translocation of Breast Cancer.: Sung Im Do, In Gu Do, Gou Young Kim, Sun Lee, Youn Wha Kim, Yong Koo Park, Juhie Lee, Sung Jig Lim; Korean J Pathol. 2008;42(2):75-80.

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Abstract PDF: BACKGROUND
Embryonic lethal abnormal vision (ELAV)-like protein HuR is known to stabilize mRNA through binding AU-rich elements in the 3'-untranslated region. Recent studies show that HuR expression is associated with the expression of several genes including cyclooxygenase-2 (COX-2). HuR exists predominantly in the nucleus, but cytoplasmic translocation of HuR is thought to be more important for its activity. COX-2 is a well-known enzyme that promotes tumor growth.
METHODS
To evaluate the correlation of HuR and COX-2 expression, we analyzed expression of HuR and COX-2 in 91 cases of breast cancer using immunohistochemistry.
RESULTS
Nuclear and cytoplasmic expression of HuR was seen in 76 (83.5%) and 19 (20.9%) of 91 cases respectively. COX-2 immunoreactivity was seen in 54 (59.4%) cases. Cytoplasmic HuR expression showed significant correlation with COX-2 expression (p=0.001). Nuclear HuR showed no correlation with COX-2 expression or other clinicopathological parameters. COX-2 expression is significantly associated with tumor grade (p=0.028). COX-2 (p=0.092) and cytoplasmic (p=0.569) and nuclear HuR (p=0.247) expression showed no correlation with survival.
CONCLUSIONS
These results suggest that cytoplasmic HuR expression is associated with COX-2 expression in breast cancer and cytoplasmic location of HuR might contribute to the stabilization of COX-2 mRNA.

Expression of the GLUT1 and p53 Protein in Atypical Mucosal Lesions Obtained from Gastric Biopsy Specimens.: In Gu Do, Youn Wha Kim, Yong Koo Park; Korean J Pathol. 2006;40(1):32-38.

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Abstract PDF: BACKGROUND
The diagnosis of atypical mucosal lesions by performing hematoxylin-eosin staining is too subjective, and it is also subject to considerable inter-observer variation. There is a need for reliable immunohistochemical markers that can give reproducible results and that are not subject to individual interpretation.
METHODS
We reviewed a total of 199 cases of gastric biopsy specimens, which were all diagnosed as atypical mucosal lesions, and 124 cases of the adenocarcinomas specimens had been classified from category 1 (C1) to C5 according to the Vienna classification. We also examined the immunohistochemical expressions of the glucose transporter GLUT1 and the p53 protein in the gastric biopsy specimens to determine if they were useful markers for differentiatial diagnosis under the Vienna classifications.
RESULTS
None of the specimens in categories C1 to C3 showed GLUT1 expression, but 10.1% of the C4 specimens and 25.0% of the C5 specimens were GLUT1-positive (p<0.05). The expression of p53 was undetectable in the C1 specimens, but this was expressed in 2.9% of the C2 specimens, 15.6% of the C3 specimens, 37.8% of the C4 specimens, and 65.3% of the C5 specimens (p<0.05).
CONCLUSIONS
The Vienna classification is very applicable to the gastric biopsy specimens of the atypical mucosal lesions, and the GLUT1 and p53 expressions are candidates as highly useful markers to differentiate the Vienna C4 lesions from the C3 and C5 lesions.

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