Journal of Pathology and Translational Medicine

Original Article

Prognostic Utility of Histological Growth Patterns of Colorectal Lung Oligometastasis: Son Jae Yeong, Min Gyoung Pak, Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh; J Pathol Transl Med. 2018;52(2):98-104. Published online February 12, 2018; DOI: https://doi.org/10.4132/jptm.2017.12.27

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Background
Patients with resectable colorectal lung oligometastasis (CLOM) demonstrate a heterogeneous oncological outcome. However, the parameters for predicting tumor aggressiveness have not yet been fully investigated in CLOM. This study was performed to determine the prognostic value of histological growth patterns in patients who underwent surgery for CLOM.
Methods
The study included 92 patients who were diagnosed with CLOM among the first resection cases. CLOMs grow according to three histological patterns: aerogenous, pushing, and desmoplastic patterns. The growth patterns were evaluated on archival hematoxylin and eosin–stained tissue sections.
Results
The aerogenous pattern was found in 29.4% (n=27) of patients, the pushing pattern in 34.7% (n=32), the desmoplastic pattern in 6.5% (n=6), and a mix of two growth patterns in 29.4% (n=27). The size of the aerogenous pattern was significantly smaller than that of metastases with other patterns (p=.033). Kaplan-Meier analysis demonstrated that patients showing an aerogenous pattern appeared to have a poorer prognosis, which was calculated from the time of diagnosis of the CLOM (p=.044). The 5-year survival rate from the diagnosis of colorectal cancer tended to be lower in patients with an aerogenous pattern than in those who had a non-aerogenous pattern; however, the difference was marginally significant (p=.051). In the multivariate Cox analysis, the aerogenous pattern appeared as an independent predictor of poor overall survival (hazard ratio, 3.122; 95% confidence interval, 1.196 to 8.145; p=.020).
Conclusions
These results suggest that the growth patterns may play a part as a histology-based prognostic parameter for patients with CLOM.

Citations

Citations to this article as recorded by

Predicting liver metastases growth patterns: Current status and future possibilities
Rui Caetano Oliveira, Henrique Alexandrino, Maria Augusta Cipriano, Filipe Caseiro Alves, José Guilherme Tralhão
Seminars in Cancer Biology.2021; 71: 42. CrossRef
Histological growth patterns and molecular analysis of resected colorectal lung metastases
Emanuela Pilozzi, Damiano Fedele, Andrea Montori, Laura Lorenzon, Valentina Peritore, Giorgia Mannocchi, Nikta Bagheri, Chiara Leone, Antonio Palumbo, Michela Roberto, Giulio Ranazzi, Erino Rendina, Genoveffa Balducci, Mohsen Ibrahim
Pathology - Research and Practice.2021; 222: 153414. CrossRef

Brief Case Report

One Case of a BRCA1 Germ Line Mutation Ovarian Carcinoma Patient Based on Abnormal Immunohistochemistry Finding: Hyun Joo Kim, Jung Min Park, Hyoun Wook Lee, Eun Hee Lee, Min Kyu Kim; Korean J Pathol. 2014;48(5):379-381. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.379

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Original Articles

Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors: Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh; Korean J Pathol. 2014;48(1):17-23. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.17

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Abstract PDF

Background

Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.

Methods

Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).

Results

Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).

Conclusions

This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

Citations

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Role of microRNAs in regulating cell proliferation, metastasis and chemoresistance and their applications as cancer biomarkers in small cell lung cancer
Monu Pandey, Abhirup Mukhopadhyay, Surender K. Sharawat, Sachin Kumar
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Neuroendocrine Tumors Are Enriched in Cowden Syndrome
Alison Greidinger, Susan Miller-Samuel, Veda N. Giri, Michele Sue-Ann Woo, Saranya Akumalla, Charnita Zeigler-Johnson, Scott W. Keith, Daniel P. Silver
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Prognostic and predictive role of the PI3K–AKT–mTOR pathway in neuroendocrine neoplasms
P. Gajate, T. Alonso-Gordoa, O. Martínez-Sáez, J. Molina-Cerrillo, E. Grande
Clinical and Translational Oncology.2018; 20(5): 561. CrossRef
Genetic and epigenetic drivers of neuroendocrine tumours (NET)
Annunziata Di Domenico, Tabea Wiedmer, Ilaria Marinoni, Aurel Perren
Endocrine-Related Cancer.2017; 24(9): R315. CrossRef
Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung
Pietro Di Fazio, Moritz Maass, Silvia Roth, Christian Meyer, Joana Grups, Peter Rexin, Detlef K Bartsch, Andreas Kirschbaum
Tumor Biology.2017; 39(10): 101042831772841. CrossRef
The regulatory role of aberrant Phosphatase and Tensin Homologue and Liver Kinase B1 on AKT/mTOR/c-Myc axis in pancreatic neuroendocrine tumors
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Oncotarget.2017; 8(58): 98068. CrossRef
Pulmonary atypical carcinoid in a patient with Cowden syndrome
Hiroaki Tsunezuka, Kaori Abe, Junichi Shimada, Masayoshi Inoue
Interactive CardioVascular and Thoracic Surgery.2016; 22(6): 860. CrossRef
Differential miRNA-Expression as an Adjunctive Diagnostic Tool in Neuroendocrine Tumors of the Lung
Melanie Demes, Christoph Aszyk, Holger Bartsch, Joachim Schirren, Annette Fisseler-Eckhoff
Cancers.2016; 8(4): 38. CrossRef
microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway
Yu-Bin Meng, Xue Li, Zhao-Yang Li, Jin Zhao, Xu-Bo Yuan, Yu Ren, Zhen-Duo Cui, Yun-De Liu, Xian-Jin Yang
Journal of Orthopaedic Research.2015; 33(7): 957. CrossRef
Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21
Song Yan, Gang Liu, Changyan Pei, Wenqing Chen, Pei Li, Qiang Wang, Xintian Jin, Jiajia Zhu, Mengzhu Wang, Xiyu Liu
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Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas: Hyoun Wook Lee, Ki Hoon Song, Jin Woo Hong, Su Young Jeon, Dong Yeob Ko, Ki Ho Kim, Hyuk Chan Kwon, Suee Lee, Sung Hyun Kim, Dae Cheol Kim; Korean J Pathol. 2012;46(3):246-252. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.246

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Abstract PDF

Background

This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters.

Methods

We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors.

Results

The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005).

Conclusions

Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

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Clinicopathological Features of Patients with Malignant Melanoma Diagnosis and Prognostic and Predictive Importance of Neuthrophil-Lymphocyte Ratio
Yasemin SAĞDIÇ KARATEKE, Lütfiye DEMİR, Murat DİNÇER, Bülent YILDIZ
OSMANGAZİ JOURNAL OF MEDICINE.2023;[Epub] CrossRef
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Changhee Park, Miso Kim, Min Jung Kim, Hyeongmin Kim, Chan-Young Ock, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jong-Il Kim, Dae Seog Heo
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Kyueng-Whan Min, Ji-Young Choe, Mi Jung Kwon, Hye Kyung Lee, Ho Suk Kang, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Yun Joong Kim, Nan Young Kim, Ho Young Kim
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Giulia M. Ravaioli, Emi Dika, Martina Lambertini, Marco A. Chessa, Pier Alessandro Fanti, Annalisa Patrizi
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Abdlsattar Zebary, Katarina Omholt, Ismini Vassilaki, Veronica Höiom, Diana Lindén, Lisa Viberg, Lena Kanter-Lewensohn, Carolina Hertzman Johansson, Johan Hansson
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The Interobserver Variability for Diagnosing Pulmonary Carcinoid Tumor.: Chang Hun Lee, Hee Kyung Chang, Hyoun Wook Lee, Dong Hoon Shin, Mee Sook Roh; Korean J Pathol. 2010;44(3):267-271.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.267

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Abstract PDF

BACKGROUND
Although the grade of pulmonary carcinoid tumor is routinely reported in pathology practice, there is a paucity of data on the level of agreement between pathologists.
METHODS
Data for 30 cases of surgically resected pulmonary tumors diagnosed as carcinoid tumors (19 typical carcinoids [TCs] and 11 atypical carcinoids [ACs]) were retrieved from four university hospitals. These cases were independently evaluated by five pathologists and were classified according to the 2004 World Health Organization (WHO) classification. Agreement was regarded as "unanimous" if all five pathologists agreed, and as a "majority" if four agreed. The kappa statistic was calculated to measure the degree of agreement between pathologists.
RESULTS
Unanimous agreement was achieved for 50.0% and a majority agreement for 83.3% of the 30 cases. The range of the kappa values extended from 0.37 to 0.89. After a consensus meeting, there was disagreement between the original diagnosis by each institute and the consensus diagnosis by the five pathologists for 40.0% of the 30 cases. Based on the consensus diagnosis, the agreement was greater for TCs than that for ACs.
CONCLUSIONS
Discriminating carcinoid tumors is subject to interobserver variability. This study indicates that there is a need for more careful standardization and application of diagnostic criteria for making the diagnosis of pulmonary carcinoid tumor.

Citations

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Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project
É. Mathian, Y. Drouet, A. Sexton-Oates, M.G. Papotti, G. Pelosi, J.-M. Vignaud, L. Brcic, A. Mansuet-Lupo, F. Damiola, C. Altun, J.-P. Berthet, C.B. Fournier, O.T. Brustugun, G. Centonze, L. Chalabreysse, V.T. de Montpréville, C.M. di Micco, E. Fadel, N.
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Limited additive value of the Ki‐67 proliferative index on patient survival in World Health Organization‐classified pulmonary carcinoids
Dorian R A Swarts, Martina Rudelius, Sandra M H Claessen, Jack P Cleutjens, Stefan Seidl, Marco Volante, Frans C S Ramaekers, Ernst J M Speel
Histopathology.2017; 70(3): 412. CrossRef
Interobserver Variability for the WHO Classification of Pulmonary Carcinoids
Dorian R.A. Swarts, Robert-Jan van Suylen, Michael A. den Bakker, Matthijs F.M. van Oosterhout, Frederik B.J.M. Thunnissen, Marco Volante, Anne-Marie C. Dingemans, Marc R.M. Scheltinga, Gerben P. Bootsma, Harry M.M. Pouwels, Ben E.E.M. van den Borne, Fran
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Lung parenchymal invasion in pulmonary carcinoid tumor: An important histologic feature suggesting the diagnosis of atypical carcinoid and poor prognosis
Sang Yun Ha, Jae Jun Lee, Junhun Cho, Jiyeon Hyeon, Joungho Han, Hong Kwan Kim
Lung Cancer.2013; 80(2): 146. CrossRef
CD44 and OTP Are Strong Prognostic Markers for Pulmonary Carcinoids
Dorian R.A. Swarts, Mieke E.R. Henfling, Leander Van Neste, Robert-Jan van Suylen, Anne-Marie C. Dingemans, Winand N.M. Dinjens, Annick Haesevoets, Martina Rudelius, Erik Thunnissen, Marco Volante, Wim Van Criekinge, Manon van Engeland, Frans C.S. Ramaeke
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Altered expression of microRNA miR‐21, miR‐155, and let‐7a and their roles in pulmonary neuroendocrine tumors
Hyoun Wook Lee, Eun Hee Lee, Seung Yeon Ha, Chang Hun Lee, Hee Kyung Chang, Sunhee Chang, Kun Young Kwon, Il Seon Hwang, Mee Sook Roh, Jeong Wook Seo
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Differential expression of forkhead box M1 and its downstream cyclin‐dependent kinase inhibitors p27kip1 and p21waf1/cip1 in the diagnosis of pulmonary neuroendocrine tumours
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Immunohistochemical Expression of the Sodium/Iodide Symporter in Patients with Primary Lung Cancer.: Hyoun Wook Lee, Do Young Kang, Phil Jo Choi, Doo Kyung Yang, Ki Nam Kim, Kyung Eun Lee, Mee Sook Roh; Korean J Pathol. 2006;40(2):81-85.

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Abstract PDF: BACKGROUND
The sodium/iodide symporter (NIS) is a membrane glycoprotein that facilitates the uptake of iodine by thyroid follicular cells. Although the use of radioiodide is essential for the diagnosis and treatment of thyroid diseases, few studies have been conducted to investigate the use of NIS-mediated radioiodide accumulation in lung cancer. We evaluated the expression of NIS by immunohistochemistry in order to examine the diagnostic or therapeutic feasibility of using radioiodide in the treatment of primary lung cancer.
METHODS
Immunohistochemistry for NIS was performed in 139 lung cancers. The expression pattern of NIS was compared with the clinicopathological characteristics of the tumors.
RESULTS
NIS immunoreactivity was detected in 75 (54.0%) of the 139 cases. Twenty-three (37.7%) of the 61 squamous cell carcinomas, 49 (76.6%) of the 64 adenocarcinomas, 2 (40.0%) of the 5 small cell carcinomas, and 3 (33.3%) of the 9 other carcinomas showed positive NIS immunoreactivity. The expression of NIS was significantly associated with the histologic type (p<0.001), but it did not correlate with tumor size, lymphovascular invasion or lymph node metastasis.
CONCLUSIONS
The presence of NIS was detected in lung cancer tissue using immunohistochemistry. Lung cancer potentially could be targeted with radioiodide for both diagnosis and treatment, especially in cases of adenocarcinoma.

Case Report

Peripheral Micronodular Squamous Cell Carcinoma of the Lung Unexpectedly Discovered after an Operation for Spontaneous Pneumothorax: A Case Report.: Hyoun Wook Lee, Phil Jo Choi, Mee Sook Roh; Korean J Pathol. 2005;39(6):424-427.

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Abstract PDF: The occurrence of lung cancer in patients suffering with pneumothorax is very rare, especially in the absence of any radiological changes that would suggest neoplasia after the pulmonary reexpansion. We have experienced a case of a 60-year-old male who presented with lung cancer that was discovered by chance after an operation for his pneumothorax. The resected lung tissue showed a 0.3 cm-sized, peripheral squamous cell carcinoma associated with a bulla. The tumor was not macroscopically detected on the first thoracotomy that was performed for the treatment of the pneumothorax. The micronodular cancer was diagnosed after the histological examination of the resected bulla. The patient has been doing well with no evidence of tumor recurrence during the fifteen months follow-up. This case shows that we should always be vigilant for associated lung cancer when we examine the lung tissue after the operation for pneumotherax.

Original Article

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

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