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LETTER TO THE EDITOR
Year : 2022  |  Volume : 18  |  Issue : 3  |  Page : 862-863

Both Kras gene mutation and Her2 gene mutation tend to exist in an inverse manner but not mutually exclusive in mucinous ovarian carcinoma: An analysis of 21 taiwanese women


1 Department of Pathology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan
2 Department of Statistics and Informatics Science, Providence University, Taichung, Taiwan
3 Department of Pathology, Chung-Shan Medical University, Chung Shan Medical University Hospital, Taichung, Taiwan
4 Department of Pathology, Chung-Shan Medical University, Chung Shan Medical University Hospital; Department of Obstetrics and Gynecology, Chung-Shan Medical University, Chung Shan Medical University Hospital, Taichung, Taiwan

Date of Submission20-Sep-2020
Date of Acceptance21-Feb-2021
Date of Web Publication01-Mar-2022

Correspondence Address:
Chih-Ping Han
Department of Pathology, Chung-Shan Medical University and Chung Shan Medical University Hospital, Taichung; Department of Obstetrics and Gynecology, Chung-Shan Medical University and Chung-Shan Medical University Hospital, Taichung
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1358_20

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How to cite this article:
Koo CL, Lee MY, Chao WR, Han CP. Both Kras gene mutation and Her2 gene mutation tend to exist in an inverse manner but not mutually exclusive in mucinous ovarian carcinoma: An analysis of 21 taiwanese women. J Can Res Ther 2022;18:862-3

How to cite this URL:
Koo CL, Lee MY, Chao WR, Han CP. Both Kras gene mutation and Her2 gene mutation tend to exist in an inverse manner but not mutually exclusive in mucinous ovarian carcinoma: An analysis of 21 taiwanese women. J Can Res Ther [serial online] 2022 [cited 2022 Aug 10];18:862-3. Available from: https://www.cancerjournal.net/text.asp?2022/18/3/862/338861



Sir,

We identified that both the frequencies of either KRAS or HER2 gene mutation disagreed in primary mucinous ovarian carcinoma (mOC). This kind of tumor (i.e., mOC) is extremely rare, accounting for 2%–4% of all epithelial ovarian carcinomas. For years, there has been much discussion that mOC seems to be a unique disease owing to its specific biologic signatures. Oncogenes with activating mutations might be therapeutically targetable. We aimed to analyze the possible relationship between KRAS and HER2 gene alterations in 21 Taiwanese women with mOC.

In 2016, we presented that KRAS (human VKi-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation rate was 61.90% (n = 13/21) in primary mOC. Although our solid data was similar to that reported by Anglesio and Mackenzie, we elucidated that the ~100% KRAS-mutant frequency reported by Jayson et al. (2014; Lancet) was too exaggerated to be applicable to all populations.[1] Our earlier findings showed that two cases (50%) had wild-type Her2 gene, whereas the other two cases (50%) had Her2 gene missense mutations at that time, using four cases of Her2 FISH (+) mOC.[2],[3] However, the case number of that report was too small to faithfully take to mean the true result. After expanding the sample size, we identified that both the Her2 mutation rate and Her2 amplification rate were the same as 33.33% (n = 7/21; n = 7/21), independently. Nonetheless, their co-occurrence rate was 42.86% (n = 3/7).[4]

Genomic DNAs extracted from formalin-fixed, paraffin-embedded tissue blocks of these 21 cases of mOC were re-evaluated. All the donors' identities have been permanently deleted. Both the KRAS and HER2 gene mutations were detected using the same methods described previously.[3],[5]

When a contingency table of the results of both KRAS and HER2 gene mutations is drawn up, the frequencies of the agreement between the two oncogene mutations are shown along the diagonal of [Table 1] We present that both the KRAS and HER2 gene mutation rates were 61.90% (n = 13/21) and 33.33% (n = 7/21), respectively. The results revealed that both of them were negative in agreement (kappa = −0.412) and very close to the significant level (P = 0.056).
Table 1: Contingency table of frequencies showing the comparison of both Kras and Her2 mutations in mucinous ovarian carcinoma

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Even though the negative kappa would indicate agreement worse than that expected by chance, our findings indicated that both KRAS and HER2 gene mutations tend to exist in an inverse manner but not mutually exclusive. However, once the two gene mutations coexist, they may even have a synergistic effect in tumorigenesis.

It is suggested that selected genetic alterations such as KRAS and Her2 gene-activating mutations involving Her2-driven RAS/mitogen-activated protein kinase signaling pathway can exist in mOC. In future, targeted therapy may be worth testing in such patients who have mOC with advanced stages.

Financial support and sponsorship

This work was supported by Chung Shan Medical University Hospital (CSH-2019-C-028 and CSH-2020-C-029), Taichung, Taiwan.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Chang KL, Lee MY, Chao WR, Han CP. The status of Her2 amplification and Kras mutations in mucinous ovarian carcinoma. Hum Genomics 2016;10:40.  Back to cited text no. 1
    
2.
Morice P, Gouy S, Leary A. Mucinous ovarian carcinoma. N Engl J Med 2019;380:1256e66.  Back to cited text no. 2
    
3.
Lin WL, Kuo WH, Chen FL, Lee MY, Ruan A, Tyan YS, et al. Identification of the coexisting HER2 gene amplification and novel mutations in the HER2 protein-overexpressed mucinous epithelial ovarian cancer. Ann Surg Oncol 2011;18:2388-94.  Back to cited text no. 3
    
4.
Chiu HH, Chao WR, Chen CK, Lee YJ, Lee MY, Han CP. The Her2 gene aberrations in mucinous ovarian carcinoma: Analysis of twenty-one cases. Taiwan J Obstet Gynecol 2020;59:346-7.  Back to cited text no. 4
    
5.
Lee YJ, Lee MY, Ruan A, Chen CK, Liu HP, Wang CJ, et al. Multipoint Kras oncogene mutations potentially indicate mucinous carcinoma on the entire spectrum of mucinous ovarian neoplasms. Oncotarget 2016;7:82097-103.  Back to cited text no. 5
    



 
 
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