Immunohistochemical Analysis for Therapeutic Targets and Prognostic Markers in Low-Grade Endometrial Stromal Sarcoma

Kim, Kyu-Rae; Nam, Joo‐Hyun

doi:10.1097/igc.0b013e3182738361

Cited by 21 publications

(23 citation statements)

References 21 publications

(20 reference statements)

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“…Another popular proliferation biomarkers is Ki-67 which in one study was expressed in 2 of 11 LGESS and predicted recurrence [21]. In agreement with this, Ki-67 and P53 expression occurred in 54% and 10% of LGESS (total 39 cases) and this also was associated with worse survival [22]. Although the pre-2003 diagnostic criteria were used in the latter two studies, it might be that increased proliferation in rigorously WHO2003 defined ESS, Low Grade tumors plays a prognostic role.…”

Section: Introductionmentioning

confidence: 62%

Can Proliferation Biomarkers Reliably Predict Recurrence in World Health Organization 2003 Defined Endometrial Stromal Sarcoma, Low Grade?

et al. 2013

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An estimated 1500–3000 invasive Endometrial Stromal Sarcomas (ESS) cases annually occur worldwide. Before 2003, ESS was divided as low and high grade ESS based on mitotic activity. In 2003 the WHO changed the names, excluded mitoses and made nuclear atypia and necrosis the essential diagnostic criteria to distinguish ESS, Low Grade (ESS-LG, recurrence-free survival >90%) and Undifferentiated Endometrial Sarcoma (UES, poor prognosis). We have evaluated in WHO2003 defined ESS-LG whether proliferation biomarkers predict recurrence. Using survival analysis, the prognostic value of classical mitosis counts (Mitotic Activity Index, MAI) in haematoxyllin-eosin (H&E) sections, and immunohistochemical proliferation biomarkers (Ki-67 and PhosphoHistone-3 (PPH3)) were examined in 24 invasive endometrial stromal sarcomas. Three of 24 (12.5%) ESS-LG recurred. The MAI, PPH3 and Ki-67 were all prognostic (P = 0.001, 0.002 and 0.03). MAI values were >3 in the recurrent cases, but never exceeded 10 (the classical threshold for low and high grade). Non-recurrent cases had 0≤MAI≤3. PPH3 and Ki67 counts can be easier to perform than MAI and therefore helpful in the diagnosis of ESS, Low Grade. In conclusion, in this small study of WHO2003 defined ESS-LG, high levels of proliferation as measured by MAI, PPH3 and Ki-67 are predictive of recurrence. Larger studies are required to confirm these results.

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Section: Introductionmentioning

confidence: 62%

Can Proliferation Biomarkers Reliably Predict Recurrence in World Health Organization 2003 Defined Endometrial Stromal Sarcoma, Low Grade?

et al. 2013

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“…19 The other study examined 39 low-grade endometrial stromal sarcomas and reported 82% (32 of 39) positivity in these tumors, 20 However, the positive tumors were also reported to show only very focal KIT immunostaining (o5% based on the representative KIT immunostaining image). 20 It is unclear what accounted for greater frequency of KIT positivity in this larger study as the primary antibody (Dako antibody for all) or the dilution used did not appear to be a contributing factor. Among the four studies evaluating KIT staining in high-grade endometrial stromal sarcomas/ undifferentiated endometrial sarcomas, a total of 7 out of 18 tumors (39%) showed focal (o30%) positivity.…”

Section: Discussionmentioning

confidence: 99%

Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement

et al. 2014

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Endometrial stromal sarcomas with the YWHAE-NUTM2A/B genetic fusion characteristically contain high-grade round to epithelioid cell component that is strongly and diffusely cyclin D1-positive and it may or may not show an associated low-grade fibroblastic/myxoid cell component. They are clinically more aggressive than endometrial stromal sarcomas with the JAZF1-SUZ12 genetic fusion and frequently demonstrate extrauterine extension at initial clinical presentation. In this setting, the tumor may be misdiagnosed as gastrointestinal stromal tumor. This study examines the expression of KIT and ANO1 in 14 YWHAE-NUTM2A/B tumors by immunohistochemistry. Staining localization was determined as membranous and/or cytoplasmic, and the staining intensity was assessed (negative, weak, moderate and strong). Of the 14 tumors, 6 contained only a high-grade round cell component, 2 only a low-grade fibroblastic component and 6 had both components in the slides evaluated. The high-grade round cell component displayed moderate to strong membranous/cytoplasmic KIT staining in all tumors (12 of 12). The low-grade fibroblastic cell component showed only weak cytoplasmic KIT staining in 3 of 8 tumors. In contrast, ANO1 was negative in all 14 neoplasms, irrespective of the component evaluated. Sanger sequencing analysis (exons 9, 11, 13 and 17) and Ampliseq Cancer Panel mutation screen (Ion Torrent) demonstrated no KIT mutations in three KIT-positive YWHAE-NUTM2A/B tumors. This study shows that the high-grade round cell component of YWHAE-NUTM2A/B endometrial stromal sarcoma consistently expresses KIT but lacks KIT hotspot mutations. KIT expression may represent a potential diagnostic pitfall in the evaluation of YWHAE-NUTM2A/B endometrial stromal sarcoma presenting with pelvic/ abdominal mass, particularly in situations where its uterine origin is not definitive, and thus a panel of antibodies that includes ANO1 and cyclin D1 is necessary.

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“…The protein encoded by MKI67 gene is widely used as a marker of proliferation in routine pathological investigations and the nuclear protein Ki67 is an established prognostic marker in cancer (101)(102)(103)(104)(105). The prognostic value of Ki67 in mesothelioma is known since 1998 when it has been reported a statistically significant difference between the survival of patients having a low and high Ki67 index (P<0.001) (106); subsequently other studies confirmed its prognostic significance (70,71).…”

Section: Clinical Implications Of Overexpressed Genes In Mpmmentioning

confidence: 79%

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

2018

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Malignant pleural mesothelioma (MPM) is a very aggressive cancer poorly responsive to current therapies. MPM patients have a very poor prognosis with a median survival of less than one year from the onset of symptoms. The biomarkers proposed so far do not lead to a sufficiently early diagnosis for a radical treatment of the disease. Thus, the finding of novel diagnostic and prognostic biomarkers and therapeutic targets is needed. Gene overexpression has been frequently associated with a malignant phenotype in several cancer types; therefore the identification of overexpressed genes may lead to the detection of novel prognostic or diagnostic marker and to the development of novel therapeutic approaches, based on their inhibition. In the last years, several overexpressed genes have been identified in MPM through gene expression profiling techniques: among them it has been found a group of 51 genes that resulted overexpressed in more than one independent study, revealing their consistency among studies. This article reviews the clinical implications of confirmed overexpressed genes in MPM described so far in literature.

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Immunohistochemical Analysis for Therapeutic Targets and Prognostic Markers in Low-Grade Endometrial Stromal Sarcoma

Cited by 21 publications

References 21 publications

Can Proliferation Biomarkers Reliably Predict Recurrence in World Health Organization 2003 Defined Endometrial Stromal Sarcoma, Low Grade?

Can Proliferation Biomarkers Reliably Predict Recurrence in World Health Organization 2003 Defined Endometrial Stromal Sarcoma, Low Grade?

Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

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