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The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios

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Abstract

Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.

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Abbreviations

BML:

Benign metastasizing leiomyoma

BMLs:

Benign metastasizing leiomyomas

miRNA:

MicroRNA

miRNAs:

MicroRNA

FFPE:

Formalin-fixed paraffin-embedded

EGFL7:

Epidermal growth factor-like domain 7

ER:

Estrogen receptor

PR:

Progesterone receptor

SMA:

Smooth muscle actin

MVD:

Microvascular density

alfa-SMA:

Alfa-smooth muscle actin

MSA:

Muscle-specific actin

CTR:

Control group

MCF-7:

Michigan cancer foundation-7

ERBB2:

Erb-B2 receptor tyrosine kinase 2

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Authors and Affiliations

  1. Thoracic Surgery, Department of Medicine and Surgery, University Hospital of Parma, Viale Gramsci 14, 43126, Parma, Italy

    Luigi Ventura, Sara Cattadori, Luca Ampollini & Paolo Carbognani

  2. Pathology Unit, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy

    Letizia Gnetti & Giovanna Giordano

  3. Department of Medicine and Surgery, University of Parma, Parma, Italy

    Maurizio Rossi, Massimo Corradi & Paola Mozzoni

  4. Medical Oncology, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy

    Marcello Tiseo, Roberta Minari & Alessandro Leonetti

  5. Section of Radiology, Diagnostic Department, University Hospital of Parma, Parma, Italy

    Mario Silva & Gianluca Milanese

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  1. Luigi Ventura
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Contributions

Conception and design: LV, LG and PM. Administrative support: MR and MC. Provision of study materials or patients: LA. Collection and assembly of data: SC and AL. Data analysis and interpretation: LV, LG, MR, PM and GG. Manuscript writing: LV, MS, GM and RM. Final approval of manuscript: MT and PC.

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Correspondence to Luigi Ventura.

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The study design was approved by the Local Ethics Committees (Comitato Etico dell’Area Vasta Emilia Nord—Protocol Number: LEIO2018-35842).

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Ventura, L., Gnetti, L., Rossi, M. et al. The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios. Mol Biol Rep 48, 3485–3494 (2021). https://doi.org/10.1007/s11033-021-06322-z

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