Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment: Jaewon Hyung, Hyung-Don Kim, Min-Hee Ryu, Young Soo Park, Meesun Moon, Yoon-Koo Kang; Cancer Res Treat. 2024;56(1):199-207. Published online June 20, 2023; DOI: https://doi.org/10.4143/crt.2023.490

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Purpose
Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients.
Materials and Methods
We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics.
Results
The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%).
Conclusion
Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.

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Targeting HER2 in Gastroesophageal Cancer: A New Appetite for an Old Plight
Antonella Cammarota, Rachel Woodford, Elizabeth C. Smyth
Drugs.2025; 85(3): 361. CrossRef

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Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions: Si-Hyung Lee, Jee Eun Kim, Hong Sun Jang, Kyu Hyun Park, Byung Ho Oh, Sang Joon Shin, Kee Yang Chung, Mi Ryung Roh, Sun Young Rha; Cancer Res Treat. 2018;50(4):1378-1387. Published online January 22, 2018; DOI: https://doi.org/10.4143/crt.2017.535

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Purpose
Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected.
Materials and Methods
In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions.
Results
Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. Conclusion
Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

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Elucidation of anti-human melanoma and anti-aging mechanisms of compounds from green seaweed Caulerpa racemosa
Danar Wicaksono, Nurpudji Astuti Taslim, Vincent Lau, Rony Abdi Syahputra, Aiman Idrus Alatas, Purnawan Pontana Putra, Trina Ekawati Tallei, Raymond Rubianto Tjandrawinata, Apollinaire Tsopmo, Bonglee Kim, Fahrul Nurkolis
Scientific Reports.2024;[Epub] CrossRef
Évolution du statut braf dans le melanome : mythe ou Réalité ?
Elicia Molines, Aurélie Haffner, Frédéric Fina, Nausicaa Malissen, L’Houcine Ouafik, Jean-Jacques Grob, Nicolas Macagno
Annales de Pathologie.2022; 42(2): 113. CrossRef
Metastatic uveal melanoma: The final frontier
Elina S. Rantala, Micaela M. Hernberg, Sophie Piperno-Neumann, Hans E. Grossniklaus, Tero T. Kivelä
Progress in Retinal and Eye Research.2022; 90: 101041. CrossRef
Variations in genetics, biology, and phenotype of cutaneous disorders in skin of color – Part I: Genetic, biologic, and structural differences in skin of color
Jessica B. Brown-Korsah, Shanice McKenzie, Deega Omar, Nicole C. Syder, Nada Elbuluk, Susan C. Taylor
Journal of the American Academy of Dermatology.2022; 87(6): 1239. CrossRef
PTEN Promoter Hypermethylation Is Associated with Breslow Thickness in Acral Melanoma on the Heel, Forefoot, and Hallux
Hae Seok Park, Jong Hoon Kim, Mi Yeon Cho, Kee Yang Chung, Mi Ryung Roh
Annals of Dermatology.2021; 33(1): 18. CrossRef
Heterogeneity of GNAQ/11 mutation inversely correlates with the metastatic rate in uveal melanoma
Chen Liang, Lan ya Peng, Ming Zou, Xuemei Chen, Yingying Chen, Hou Chen, Lirong Xiao, Naihong Yan, Junjun Zhang, Qing Zhao, Xi Huang
British Journal of Ophthalmology.2021; 105(4): 587. CrossRef
Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition
Jian-Ching Wu, Han-En Tsai, Yi-Hsiang Hsiao, Ji-Syuan Wu, Chieh-Shan Wu, Ming-Hong Tai
International Journal of Molecular Sciences.2020; 21(2): 681. CrossRef
Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations
Yeongjoo Oh, Sooyie Choi, Mi Yeon Cho, Kyoung Ae Nam, Sang Joon Shin, Jee Suk Chang, Byung Ho Oh, Mi Ryung Roh, Kee Yang Chung
Journal of the American Academy of Dermatology.2020; 83(4): 1071. CrossRef
Tumor Heterogeneity on FDG PET/CT and Immunotherapy: An Imaging Biomarker for Predicting Treatment Response in Patients With Metastatic Melanoma
Y. Sanli, J. Leake, A. Odu, Y. Xi, R. M. Subramaniam
American Journal of Roentgenology.2019; 212(6): 1318. CrossRef
BRAF and NRAS mutations and antitumor immunity in Korean malignant melanomas and their prognostic relevance: Gene set enrichment analysis and CIBERSORT analysis
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
Pathology - Research and Practice.2019; 215(12): 152671. CrossRef
Molecular and genetic diversity in melanoma of eye
N. N. Mazurenko, I. V. Tsyganova, V. V. Nazarova, I. A. Utyashev, K. V. Orlova, D. A. Ponkratova, D. V. Martinkov, L. V. Demidov
Advances in molecular oncology.2018; 5(3): 51. CrossRef

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Case Report

Intra-tumoral Metastatic Double Primary Carcinoma: Synchronous Metastatic Tumor in Lung from Breast and Thyroid Carcinoma: Lee Chun Park, Ji Yun Jeong, Jun Ho Ji, Silvia Park, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park; Cancer Res Treat. 2014;46(2):200-203. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.200

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Cases of phenotypic heterogeneity of cells within tumors have recently been reported. Here, we report on a patient with characteristic intra-tumor double primary metastases in the lung. This patient was a 40-year-old Korean woman who had been diagnosed with breast cancer (T1N0M0, estrogen receptor/progesterone receptor/HER2 +/+/+) and papillary thyroid cancer three years prior and underwent a complete surgical resection followed by appropriate adjuvant treatment with radiation, hormone, and radioactive iodine. She was recently admitted for newly developed pulmonary nodules. Metastasectomy through video-assisted thoracoscopic surgery revealed recurrent double primary cancer with two different components (metastatic ductal carcinomas from the breast and metastatic papillary carcinomas from the thyroid gland) in each pulmonary nodule in the right upper lobe and right middle lobe. To the best of our knowledge, this is the first report of simultaneous recurrent double metastasis in one organ from different primary origins.

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Risk Factors and Prognostic Implications in Synchronous Breast-Thyroid Dual Primary Cancers: A Matched Case-Control Study
Tao Li, Bin Lu, Yantao Zhang, Peng Zhang, Jun Qi, Yong Sun
Cancer Management and Research.2025; Volume 17: 997. CrossRef

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