Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas

Shikama, Ayumi; Minaguchi, Takeo; Matsumoto, Koji; Akiyama-Abe, Azusa; Nakamura, Yuko; Michikami, Hiroo; Nakao, Sari; Sakurai, Minoru; Ochi, Hiroki; Onuki, Mamiko; Satoh, Toyomi; Oki, Akinori; Yoshikawa, Hiroyuki

doi:10.1016/j.ygyno.2015.11.032

Cited by 53 publications

(78 citation statements)

References 27 publications

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“…In addition, the authors observed a trend to improved PFS in tumors with MMR mutations and a suggestion that these patients received greater benefit from adjuvant chemotherapy compared to women with normal mismatch repair. Similar results for probable germline/Lynch syndrome mismatch repair deficient tumors were observed in a smaller series of 221 ECs, with no prognostic nor predictive associations noted in the tumors with methylation events [95]. …”

Section: Mmr/msisupporting

confidence: 71%

New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care

Talhouk

McAlpine

2016

gynaecol oncol res pract

159

157

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Endometrial carcinoma (EC) is the fourth most common cancer in women in the developed world. Classification of ECs by histomorphologic criteria has limited reproducibility and better tools are needed to distinguish these tumors and enable a subtype-specific approach to research and clinical care. Based on the Cancer Genome Atlas, two research teams have developed pragmatic molecular classifiers that identify four prognostically distinct molecular subgroups. These methods can be applied to diagnostic specimens (e.g., endometrial biopsy) with the potential to completely change the current risk stratification systems and enable earlier informed decision making. The evolution of genomic classification in ECs is shared herein, as well as potential applications and discussion of the essential research still needed in order to optimally integrate molecular classification in to current standard of care.

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Section: Mmr/msisupporting

confidence: 71%

New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care

Talhouk

McAlpine

2016

gynaecol oncol res pract

159

157

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“…Similarly, research by Shikama et al demonstrated that patients with MMR protein deficiency had more favorable survival outcomes than did patients with sporadic EC . Germline mutations in MSH2 , MSH6 , PMS2 , or MHL1 (and absent MHL1 methylation) were associated with younger age of onset, superficial tumor invasion, and early‐stage disease, whereas sporadic endometrial cancer was the opposite.…”

Section: Treatment Of Endometrial Carcinoma With Mutated Mmrmentioning

confidence: 94%

“…51 Endometrial cancer patients with sporadic mutations in MMR proteins typically present at a more advanced stage, with larger, FIGURE 1 Algorithm for universal Lynch syndrome screening in newly diagnosed endometrial cancer higher grade tumors, and more lymph nodes involvement. 60 Germline mutations in MSH2, MSH6, PMS2, or MHL1 (and absent MHL1 methylation) were associated with younger age of onset, superficial tumor invasion, and early-stage disease, whereas sporadic endometrial cancer was the opposite. Although these mutations also predisposed patients to having other LS-associated malignancies, they were also more sensitive to adjuvant immune therapy than sporadic EC (with nonmutated MMR genes), resulting in an overall more favorable prognosis.…”

Section: Testing For Lynch Syndromementioning

confidence: 99%

The practice of universal screening for Lynch syndrome in newly diagnosed endometrial carcinoma

Wang

McCracken

et al. 2018

Health Science Reports

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BackgroundLynch syndrome (LS) accounts for 5% of all endometrial cancer (EC) cases and 4% of all lifetime risk of developing colorectal cancer. While current guidelines recommend LS screening for all patients with newly diagnosed colorectal cancer, there is no such guideline for screening patients with EC.DiscussionThis review addresses LS screening and discusses algorithms for testing patients in the setting of newly diagnosed EC.ConclusionThe successful diagnosis of LS has important implications, including prevention of LS‐associated cancers among relatives and immunotherapy recommendations for patients with advanced EC and loss of expression of mismatch repair immunohistochemistry and microsatellite instability positive following failure of traditional treatment.

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“…The second category, hypermutated/MSI, has been better characterized over many years; features described as Lynch syndrome‐related are ambiguous morphology and combinations of histotypes (including the presence of an undifferentiated component), isthmic location and lymphocytic infiltrates . MSI‐related tumours demonstrate superior responses to adjuvant therapy and are potential candidates for immunomodulatory therapies …”

Section: Uterusmentioning

confidence: 99%

The changing landscape of gynaecological cancer diagnosis: implications for histopathological practice in the 21st century

Singh

Gilks

2016

Histopathology

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The era of molecular medicine has led to dramatically improved understanding of the genetic events that give rise to different types of cancers. In the case of gynaecological malignancies, this has resulted in distinct shifts in how these tumours are diagnosed in routine surgical pathology practice, with an increased emphasis on accurate subtype diagnosis. This has happened across all sites in the gynaecological tract and for most cell types, but in ways that are site-specific and may appear to be subtle, as in most instances the diagnostic terminology has not changed. For example, the diagnosis of clear cell carcinoma of the ovary is still in use, but the diagnostic criteria and clinical implications are different in 2017 from what they were in 2000. As a result, there can be a failure to appreciate how important these changes are and the resulting necessity of incorporating them into our daily practice. In this review we will describe changes in diagnostic surgical pathology occasioned by improved understanding of molecular events during pathogenesis, for cancers of ovary/tube, endometrium, cervix and vulva, and highlight how current practice differs from that of only a few years ago.

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Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas

Cited by 53 publications

References 27 publications

New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care

New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care

The practice of universal screening for Lynch syndrome in newly diagnosed endometrial carcinoma

The changing landscape of gynaecological cancer diagnosis: implications for histopathological practice in the 21st century

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