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MTA1 作为外阴癌的负预后标志物。

MTA1 as negative prognostic marker in vulvar carcinoma.

机构信息

Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany.

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.

出版信息

J Cancer Res Clin Oncol. 2023 Aug;149(9):6191-6201. doi: 10.1007/s00432-023-04579-4. Epub 2023 Jan 23.

DOI:10.1007/s00432-023-04579-4
PMID:36689059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10356867/
Abstract

PURPOSE

Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis.

METHODS

A total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters.

RESULTS

MTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan-Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1.

CONCLUSIONS

MTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma.

摘要

目的

外阴癌是女性生殖道第四大常见恶性肿瘤，仅次于子宫内膜癌、卵巢癌和宫颈癌，主要影响老年妇女。2020 年，全球有超过 17000 人死于外阴癌。迄今为止，关于外阴癌的靶向治疗和预测生物标志物的数据很少。转移相关基因 MTA1 是一种转录抑制剂，可能对外阴癌有影响。研究发现，在妇科恶性肿瘤中，如乳腺癌或卵巢癌组织中，随着癌症分期的进展和 FIGO 分级的升高，MTA1 的表达显著增强，这表明 MTA1 在这些肿瘤实体的进展中起着重要作用。由于缺乏有关 MTA1 的信息及其与外阴癌的相关性，本研究主要关注 MTA1 在外阴癌中的表达及其与临床病理特征和预后的相关性。

方法

对 157 例外阴癌石蜡包埋组织进行免疫组织化学染色，用免疫反应评分法检测 MTA1 的表达。随后，将这些数值与临床病理参数相关联。

结果

研究发现，94%的患者细胞质中存在 MTA1 表达，91%的细胞核中存在 MTA1 表达。与角化型鳞状细胞癌和疣状型外阴癌相比，非角化型鳞状细胞癌和湿疣样型外阴癌的细胞质中 MTA1 的表达显著增加。细胞核中 MTA1 的高表达与肿瘤较大的大小以及较高的 FIGO 分级相关。此外，与 p16 阳性外阴癌相比，p16 阴性外阴癌的核 MTA1 表达更高。令人惊讶的是，Kaplan-Meier 分析显示，核内无 MTA1 表达的肿瘤样本的无病生存率显著降低。

结论

MTA1 被确定为与晚期肿瘤分期和 FIGO 分级相关的外阴癌的负预后标志物。一种可能的解释是，本研究中使用的抗体不能与 MTA 末端区域的可能突变结合，导致免疫组织化学染色阴性，这与外阴癌患者的早期复发有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/e8041a197d9a/432_2023_4579_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/2ce8c88b7e8a/432_2023_4579_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/e8041a197d9a/432_2023_4579_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/47d556b7dbba/432_2023_4579_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/b6d27823fb64/432_2023_4579_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/365a7cb0ea83/432_2023_4579_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/ba489ed89f5b/432_2023_4579_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/50a52d2efaf2/432_2023_4579_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/c8d666c4caad/432_2023_4579_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/2ce8c88b7e8a/432_2023_4579_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e7/11797999/e8041a197d9a/432_2023_4579_Fig8_HTML.jpg

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LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients.LDOC1 作为外阴癌患者的负面预后标志物。
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