Etiologic heterogeneity in endometrial cancer: Evidence from a Gyneco- logic Oncology Group trial

Brinton, LouiseA.; Felix, Ashley S.; Sherman, Michael Y.; Zaino, Richard J.; McMeekin, D.; Wt, Creasman; Mutch, D.; Cohn, David E.; Walker, Joan; Moore, Robert K.

doi:10.1016/j.ygyno.2013.04.143

Cited by 3 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endometrial carcinoma (EC) is the most common female genital tract malignancy in the United States comprising a heterogeneous group of tumors that includes endometrioid carcinomas (EECs), serous carcinomas (ESCs), clear cell carcinomas, and other less common histologic subtypes (1). Molecular mapping of endometrial tumors in the last decade has shown that EECs and ESCs have been associated with mutations in PTEN, ARID1A, PIK3CA, KRAS, and CTNNB1, and TP53, PPP2R1A, and FBXW7, respectively (2,3).…”

mentioning

confidence: 99%

Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas

Matsumoto

Manrai

Rottmann

et al. 2022

International Journal of Gynecological Pathology

View full text Add to dashboard Cite

TP53 mutations are frequently identified in the copy number-high molecular subgroup of endometrial carcinomas (ECs). P53 immunohistochemistry (IHC) is a widely used surrogate marker reflecting the mutational status of TP53, and recent reports have shown ~95% concordance between the two methods in ECs. While these results are promising, studies evaluating the correlation between different p53 IHC staining patterns and comprehensive next-generation sequencing results are still limited. We compared the p53 IHC staining patterns, scored as wild-type, diffuse nuclear overexpression, null/complete absence, and cytoplasmic, to next-generation sequencing results reported by FoundationOneCDx in 43 high-grade ECs: 20 serous ECs, 9 mixed ECs with a serous component, 4 carcinosarcomas with a serous component, and 10 grade 3 endometrioid ECs. The concordance of p53 IHC and TP53 mutation status was 100% (43/43) overall, including 100% (33/33) concordance in tumors with a serous component and 100% (10/10) in endometrioid ECs. Among the 35 tumors with aberrant p53 expression the most commonly observed pattern was diffuse nuclear overexpression seen in 69% (24/35), followed by cytoplasmic staining in 17% (6/35), and complete absence of staining (null) in 14% (5/35) of tumors. Of the 6 tumors with cytoplasmic staining, 4 corresponded to missense mutations within the DNA binding domain (V157F in 2 tumors, and S127P and R280S, in 2 tumor each), while 2 corresponded to nonsense mutations in the tetramerization domain (p.E339*). Our results further support that p53 IHC can serve as an accurate predictor of TP53 alterations in ECs to aid the molecular-based tumor classification and the distinction between tumor histotypes, both of which play an important role in the assessment of clinical prognosis and therapeutic decision making. In addition, our data suggest, that the type and position of TP53 mutation may not directly correlate with the observed p53 IHC pattern in all tumors, and that there may be alternative mechanisms for cytoplasmic localization (other than mutations involving the nuclear localization domain), possibly due to conformational changes or posttranslational modifications of the aberrant p53 protein.

show abstract

mentioning

confidence: 99%

Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas

Matsumoto

Manrai

Rottmann

et al. 2022

International Journal of Gynecological Pathology

View full text Add to dashboard Cite

show abstract

“…The comparison with literature data is more delicate because of adjunction of grade 3 endometrioid EC to type II EC during the study period, because they are considered as having similar prognosis (35)(36). When performing our analyses, grade 3 endometrioid EC was included in type II ECs as reported in the latest recommendations.…”

Section: Discussionmentioning

confidence: 99%

Evolution of characteristics of women with endometrial cancer during a 40 years study period

Lorphelin¹,

Rossard²,

Rua³

et al. 2019

Journal of Gynecology Obstetrics and Human Reproduction

View full text Add to dashboard Cite

Management of inoperable endometrial cancer

2022

View full text Add to dashboard Cite

Some endometrial cancer (EMC) patients are not good candidates for primary surgery. The three major types of treatment for inoperable EMC are radiation therapy, chemotherapy, or their combination as neoadjuvant treatment before surgery. Radiation therapy alone (of different modes) has been used as the sole definitive therapeutic modality, particularly for early-stage disease that is limited to the uterine body and cervix with or without parametrial invasion. The most common treatment modality is neoadjuvant treatment before surgery. Postoperative adjuvant treatment is also occasionally used, depending mainly on the sites of the disease and the results of surgery. Data on neoadjuvant hormonal or radiation therapy are limited, with studies focusing on laboratory outcomes or having only a small number of patients. Most neoadjuvant treatments before surgery involved chemotherapy and fewer combined chemoradiotherapy. Surgery was generally performed, particularly in patients who had shown responses or at least stable disease to neoadjuvant treatment. Perioperative outcomes after neoadjuvant treatment were superior to those after primary surgery, whereas survival data were still inconsistent. Features that had or tended to have a favorable prognosis were younger age, early-stage disease, response to neoadjuvant treatment, low preoperative cancer antigen-125 level, and optimal surgery. Among different modalities of neoadjuvant treatment, which has become a frequent mode of treatment, neoadjuvant chemotherapy was more common than radiation therapy alone or chemoradiation.

show abstract

Etiologic heterogeneity in endometrial cancer: Evidence from a Gyneco- logic Oncology Group trial

Cited by 3 publications

References 37 publications

Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas

Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas

Evolution of characteristics of women with endometrial cancer during a 40 years study period

Management of inoperable endometrial cancer

Contact Info

Product

Resources

About