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

Abstract

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.

Recent Developments in Surgical Pathology of the Uterine Corpus

“…6 High-grade ESS is now defined as a tumor composed of atypical cells resembling endometrial stromal cells but lacking the degree of atypia and pleomorphism of UUS (Figure 8). 44,45 The separate identity of this high-grade ESS was further confirmed by a specific YWHAE-FAM22 gene rearrangement. 46 Undifferentiated uterine sarcomas are now defined as high-grade sarcomas lacking evidence of endometrial stromal morphology combined with severe cytologic atypia, often with multinucleated and bizarre cells and brisk mitotic activity (.20 mitoses/10 HPFs).…”

A prognosis based classification of undifferentiated uterine sarcomas: Identification of mitotic index, hormone receptors and YWHAE‐FAM22 translocation status as predictors of survival

“…The most frequent chromosomal rearrangement is the t(7;17), which results in the production of a JAZF1‐JJAZ1 fusion RNA transcript. Other genes that have been involved in fusion transcripts include the PHD finger protein 1 (PHF1) and enhancer of polycomb 1 (EPC1) …”

Molecular mechanisms of endometrial stromal sarcoma and undifferentiated endometrial sarcoma as premises for new therapeutic strategies

“…Overall, SFRP4 seems to act as a tumor suppressor gene regulating the cytosolic ß-catenin pool in the cell. Interestingly, Feng et al found that proliferation markers, such as Ki-67, are also predictive for a high recurrence of ESS [40]. By using immunostaining, Ng et al detected nuclear ß-catenin staining in 40% of ESS and suggested this method to be potentially useful for diagnosis, especially for distinguishing ESS from leiomyosarcoma, which are negative for nuclear ß-catenin [41].…”