Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential

Conconi, Donatella; Chiappa, Valentina; Perego, Patrizia; Redaelli, Serena; Bovo, Giorgio; Lavitrano, Marialuisa; Milani, Rodolfo; Dalprà, Leda; Lissoni, Andrea Alberto

doi:10.3892/or.2016.5274

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…Recent studies have suggested the use of immunohistochemical stains, including epithelial growth factor receptor, galectin-3, p16, p16INK4a, p53, MIB-1, Twist, BCL-2, estrogen, and progesterone receptors to identify uterine smooth muscle tumors with a higher risk of recurrence [1516171819]. Although recurrent tumors regarded as STUMPs are associated with diffuse immunoreactivity for p16 and p53 [2021], the number of cases in these studies are small and further studies are needed to confirm the reliability of such markers.…”

Section: Discussionmentioning

confidence: 99%

Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

et al. 2019

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Objective In this study, we aimed to evaluate the clinicopathological features, obstetric, and oncological outcomes of patients diagnosed with a uterine smooth muscle tumors of uncertain malignant potential (STUMP). Methods A dual-institutional, database review was carried out to screen patients with STUMP who were treated with upfront surgery between January 2006 and December 2017. Data including age at the time of diagnosis, recurrence rate, disease-free survival, overall survival, and fertility outcomes were retrospectively analyzed. Results Fifty-seven patients with STUMPs were included in the study. The median age at the time of diagnosis was 42 (range, 16 to 75) years. The median follow-up was 57 (range, 16 to 125) months. Eight patients (14%) had recurrence during follow-up. Recurrent STUMPs were seen in seven patients and leiomyosarcoma after 14 months in one patient. Seven patients with a recurrent STUMP survived, while the remaining patient died. Recurrence rates were similar for women who underwent myomectomy and those who underwent hysterectomy. The presence of uterine localization of tumor (subserosal vs intramural-submucosal) statistically significantly affected recurrence rates (odds ratio=5.72; 95% confidence interval=1.349–24.290; p=0.018). Ten of 27 patients who underwent myomectomy for uterine myoma had fertility desire. Seven pregnancies were recorded. Conclusions Our study results suggest that fertility-sparing approaches are feasible in patients with STUMP, although recurrence may be seen.

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Section: Discussionmentioning

confidence: 99%

Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

et al. 2019

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“…This expression pattern was the same one found in human samples. The miR-1-3p seems to modulate critical genes as Bcl-2, which regulates apoptosis [ 18 ]. Estrogen receptor 1 (ESR1), which mediates ULM development and appears to be expressed in ULMS [ 19 ] and c-MET cells, acts in tumor dissemination by activating mitogenic signaling pathways [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Oncomirs Expression Profiling in Uterine Leiomyosarcoma Cells

Almeida

Garcia

Maffazioli

et al. 2017

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile of 84 miRNAs involved in tumorigenesis in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS). Specific cell lines were cultured and qRT-PCR was performed. Thirteen miRNAs presented different expression profiles in ULM and the same thirteen in ULMS compared to MM. Eight miRNAs were overexpressed, and five were underexpressed in ULM. In ULMS cells, five miRNAs exhibited an overexpression and eight were down-regulated. Six miRNAs (miR-1-3p, miR-130b-3p, miR-140-5p, miR-202-3p, miR-205-5p, and miR-7-5p) presented a similar expression pattern in cell lines compared to patient samples. Of these, only three miRNAs showed significant expression in ULM (miR-1-3p, miR-140-5p, and miR-7-5p) and ULMS (miR-1-3p, miR-202-3p, and miR-7-5p). Our preliminary approach identified 24 oncomirs with an altered expression profile in ULM and ULMS cells. We identified four differentially expressed miRNAs with the same profile when compared with patients’ samples, which strongly interacted with relevant genes, including apoptosis regulator (BCL2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), insulin like growth factor 1 receptor (IGF1R),serine/threonine kinase (RAF1), receptor tyrosine kinase (MET), and bHLH transcription factor (MYCN). This led to alterations in their mRNA-target.

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“…In recent years, IHC has shown to improve our ability to identify and better classify AUSMT, and numerous small series have investigated the expression profiles of several biomarkers and their correlation with prognosis [25][26][27][28][29] . p16 and p53 are tumor suppressor genes that negatively regulate cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Atypical Uterine Smooth Muscle Tumors: A Retrospective Evaluation of Clinical and Pathologic Features

et al. 2017

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Background: Clinical characteristics combined with new biomarkers help discriminate between atypical uterine smooth muscle tumors (AUSMT) and leiomyosarcomas (LMS). Patients and Methods: We retrospectively collected a series of leiomyomas (LM), AUSMT, and LMS. Estrogen receptors (ER), progesterone receptors (PR), p16, Ki-67, and p53 expression were assessed by immunohistochemistry. For AUSMT patients, immunohistochemistry evaluations were performed at the time of diagnosis and at recurrences. Results: A total of 27 cases of AUSMT, 22 LM, and 31 LMS were identified. The expression of ER and PR decreased from LM to LMS (ER+: LM 95.5%, AUSMT 88.9%, LMS 41.9%, p < 0.001; PR+: LM 100%, AUSMT 88.9%, LMS 38.2%, p = 0.002). By contrast, p16 and p53 expression increased (p16+: LM 4.5%, AUSMT 40.7%, LMS 45.2%, p = 0.004; p53: LM 9.1%, AUSMT 33.3%, LMS 58.1%, p = 0.001). At a median follow-up of 33.47 months, 40.7% of patients with AUSMT experienced recurrent disease, 6 patients relapsed as AUSMT and 5 as LMS. In univariate analysis was observed that ER status (p = 0.027) and p53 expression (p = 0.015) predicted risk of relapse. Conclusions: Treatment of AUSMT should be centralized in dedicated centers. International collaborations are needed to optimize research strategy, which may lead to the identification of new useful biomarkers and to improvement in the clinical management of this rare disease.

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Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential

Cited by 16 publications

References 22 publications

Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

Oncomirs Expression Profiling in Uterine Leiomyosarcoma Cells

Atypical Uterine Smooth Muscle Tumors: A Retrospective Evaluation of Clinical and Pathologic Features

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