Journal of Pathology and Translational Medicine

Original Article

Targeted next-generation sequencing–based mutational signature analysis in endometrial cancer: utility and limitations across molecular subtypes: Uijin Kim, Ahwon Lee, Keun Ho Lee, Sung Jong Lee, Sook Hee Hong, Donghyuk Lee, Jun Kang, Miseon Lee; J Pathol Transl Med. 2026;60(6):625-634. Published online November 10, 2026; DOI: https://doi.org/10.4132/jptm.2026.09.07

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Abstract PDF Supplementary Material: Background
Molecular subtype classification is essential for staging endometrial cancer, planning adjuvant treatments, and stratifying prognosis. However, the correlation between mutational signature analysis using tumor-only targeted next-generation sequencing (NGS) data and molecular subtypes, as well as the interpretive value at the individual case level, remains inadequately characterized. Methods: We performed mutational signature analysis on tumor-only targeted NGS data from 72 endometrial cancer cases using the SATS R package. Molecular classification into four subtypes (POLE-mutated, mismatch repair deficient [MMRd], TP53-mutant, and no specific molecular profile [NSMP]) was established through a standard stepwise algorithm that integrated NGS and immunohistochemistry. Results: Out of the 72 endometrial cancers, 12 were classified as POLE-mutated, 10 as MMRd, six as TP53-mutant, and 44 as NSMP. All POLE-mutated tumors exhibited POLE-associated signatures (SBS10a/SBS10b), including cases with non-hotspot POLE exonuclease variants and tumor mutation burdens below the conventional ultramutation threshold. MMRd-associated signatures showed a broader distribution across molecular subtypes; while the summed MMRd-associated signatures were typically higher in MMRd tumors, low-level contributions were also noted in subsets of NSMP and TP53-mutant tumors. Within the POLE-mutated group, MMRd-associated signatures were more pronounced in cases displaying subclonal MMR protein loss as determined by immunohistochemistry. Conclusions: In this small, clinically selected cohort, targeted NGS-based mutational signatures provided exploratory, complementary information regarding POLE-associated mutagenesis and mixed MMR-related patterns. Overlapping signature distributions, dependence on the analytical pipeline, and the use of tumor-only targeted sequencing limit case-level interpretation. Mutational signature analysis should be interpreted in conjunction with established molecular tests and should not be used as a stand-alone classifier.

Case Report

Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women: Sung Jong Lee, Hyun Joo Choi; Korean J Pathol. 2012;46(4):395-398. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.395

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16 Crossref

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p^16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.

Citations

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Original Article

Prognostic Significance of Amplification of the c-MYC Gene in Surgically Treated Stage IB-IIB Cervical Cancer.: Tae Jung Kim, Ahwon Lee, Sung Jong Lee, Won Chul Lee, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang; Korean J Pathol. 2011;45(6):596-603.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.596

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Abstract PDF

BACKGROUND
Mutations of c-MYC have been described in cervical cancer. However, association between c-MYC gene status and its prognostic significance have not been clarified.
METHODS
Tissue microarray sections from 144 patients with stage IB-IIB cervical cancer treated by radical hysterectomy were analyzed by fluorescence in situ hybridization using a region-specific probe for c-MYC and a centromere-specific probe for chromosome 8.
RESULTS
Seventy five percent (108/144) of c-MYC gain and 6.9% (10/144) of c-MYC gene amplification were observed. c-MYC gene alteration was more frequently observed in squamous cell carcinoma than adenocarcinoma or adenosquamous carcinoma and were associated with low Ki67 labeling index (p=0.013). c-MYC amplification was not associated with clinicopathologic parameters except absence of bcl2 expression (p=0.048). Survival analysis revealed that patients with c-MYC amplification were significantly associated with higher risk of disease recurrence (p=0.007) and cancer related death (p=0.020). However, c-MYC gain was not associated with unfavorable outcome. Multivariate analysis proved c-MYC amplification as independent prognostic factors of shorter disease free survival and cancer-related death (p=0.028 and p=0.025, respectively).
CONCLUSIONS
c-MYC amplification, not gain, is an independent prognostic marker for shorter disease free and cancer specific survival in cervical cancer treated by radical hysterectomy.

Citations

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A Rare Case of Cutaneous Plasmacytosis in a Korean Male
Corey Georgesen, Meenal Kheterpal, Melissa Pulitzer
Case Reports in Pathology.2017; 2017: 1. CrossRef

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