The selected biomarker analysis in 5 types of uterine smooth muscle tumors

Abstract

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P < .01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P = .055 for PR and P = .0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P = .0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants.

Recurrent Uterine Smooth-Muscle Tumors of Uncertain Malignant Potential (STUMP): State of The Art

“…In fact, high PR expression has a statistically significant association with longer overall survival, thereby providing useful prognostic data. These results suggest that PR positivity may represent a positive prognostic factor for recurrence and survival in LMS, similarly to previously published data (29)(30)(31).…”

“…These findings were recently confirmed by Zhang et al (30). In their study, 119 cases of uterine smooth-muscle tumors were reviewed, including LMS, LM and STUMP.…”

“…In particular, more than 45% of LMS cases had a Ki-67 index of more than 66% compared with 29% of cases with an index of less than 33%. In contrast, almost 95% of all other types of smooth-muscle cell tumors were found to have a Ki-67 index less than 30% (30). On the basis of these data, the authors proposed 33% as a Ki-67 index cut-off useful for differentiating among LMS and other types of uterine smooth-muscle tumor.…”

“…In summary, no single marker may be considered exhaustive and sufficient to separate LMS from other variants but it would be appropriate to analyze an immunohistochemical panel evaluating several biomarkers such as PR, ER, Ki-67 and p53, especially in case of uterine smooth-muscle tumors with ambiguous or borderline histological features (30,31).…”

Clinical and reproductive outcomes of uterine smooth muscle tumor of uncertain malignant potential: a single-center retrospective study

“…Furthermore, high PR expression was significantly associated with longer overall survival. 20 In the current study, 75% of STUMP tumors (12/16) showed PR expression and 63% (10/16) showed ER expression. The recurrent case showed 30% Ki-67 and was negative for p53 and positive for PR and ER.…”