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. 2022 May 31;28(6):890–909. doi: 10.1093/humupd/dmac027

Table II.

BCL6 expression in human endometriosis.

Reference Sample number/patient information Methods Main results
Evans-Hoeker et al. (2016)

  • n = 20 fertile controls.

  • n = 29 endometriosis at laparoscopy.

  • n = 28 fertile controls.

  • n = 119 women with UI.

  • Exclusion criteria were age ≥40, pelvic infection/inflammation, PCOS, or fibroid tumors.

  • BCL6 expression by qPCR (Gene Expression Assays; Applied Biosystems (Foster City, CA)—assay HS00153368);

  • IHC and HSCORE with BCL6 antibody clone LN22 (Leica Biosystems).

  • BCL6 was significantly higher in the secretory phase of patients with endometriosis versus controls (P < 0.0001). Both BCL6 mRNA and protein were increased in endometrial epithelium of women with endometriosis.

  • 93.8% of BCL6 positive patients had endometriosis. A cutoff of 1.4 in HSCORE provided a likelihood ratio of 15.4 and 0.04 for positive and negative results, respectively.
Almquist et al. (2017)

  • Women with UI for >1 year.

  • n = 69:

  • n = 20 pregnant, age 36.3 ± 3.2

  • n = 49 non-pregnant, age 34.5 ± 3.9.

  • Groups based on BCL6 expression: n = 17 normal expression (age 35.6 ± 3.1; n = 11 pregnant/n = 6 non-pregnant);

  • n = 52 high expression (age 34.8 ± 3.9; n = 9 pregnant/n = 43 non-pregnant).

 Prospective cohort study, IHC and HSCORE with BCL6 antibody clone LN22 (Leica Biosystems).

  • Clinical pregnancy rate and live birth rate per transfer were compared between women with positive or negative BCL6 staining. A high BCL6 expression was defined by a histologic score (>1.4) and strongly associated with poor reproductive outcomes in IVF cycles in women with UI

  • BCL6 expression, median (range) was 0.9 (0–4) in the pregnant group and 2.1 (0.5–4.0) in the non-pregnant group (P = 0.01).

  • Staining for BCL6 was predominantly localized in the nucleus. 75.3% of patients with UI-tested positive for BCL6.
Gong et al. (2017)

  • n = 30 controls (age 32.77 ± 4.7).

  • n = 30 RIF (age 33.23 ± 5.06).

 qPCR and IHC with rabbit BCL6 antibody (1:100; cat no. bs2734R, BIOSS, Beijing, China). The mRNA and protein level of BCL6 in the endometrium during the mid-luteal phase was significantly increased in the RIF group.
Yoo et al. (2017)

  • Age 18–45.

  • For control: 21 samples from proliferative (n = 5) and secretory phase (n = 16) for WB and 23 samples from the proliferative (n = 6) and secretory (n = 17) phase for IHC.

  • For endometriosis: 54 samples from proliferative (n = 16) and secretory (n = 38) phase for WB and 57 samples for IHC.

 Results were based on the WB band intensity (BCL6 antibody 561520; BD Pharmingen, San Jose, CA) and correlation coefficient = 0.5659, P < 0.0001, between BCL6 and SIRT1 expression.

  • BCL6, KRAS and SIRT1 were co-ordinately over-expressed in eutopic endometrium of women with endometriosis and likely participated in the pathogenesis of endometriosis

  • BCL6 and SIRT1 were co-localized in the nuclei of endometrial cells, bound to and suppressed the promoter of GLI1, suggesting its role in progesterone action.
Likes et al. (2019)

  • Age 27–42, n = 85 cycles.

  • Three groups:

  • medical suppression (n = 10),

  • laparoscopy (n = 20),

  • controls (n = 54).

  • Prospective cohort study.

  • At least 1 year of UI, underwent endometrial biopsy, and IHC for BCL6 (clone LN22, Leica Biosystems), prior to embryo transfer during an ART cycle. Subjects had elevated BCL6 (HSCORE ≥ 1.4).

  • Patients with positive endometrial BCL6, defined as an HSCORE >1.4, were associated with poor IVF outcomes and recurrent miscarriage.

  • Increased endometrial BCL6 was associated with worse reproductive outcomes after embryo transfer, compared with women with endometriosis and treated with medical or laparoscopy.
Nezhat et al. (2020)

  • Age 29–47.

  • n = 72 endometriosis.

  • n = 3 with other pathologies.

  • Inclusion criteria: women of reproductive age undergoing IVF with a diagnosis of UI or recurrent pregnancy loss, endometrial biopsy with ReceptivaDx™.

  • Retrospective cohort study.

  • Patients with endometrial BCL6 overexpression underwent laparoscopic surgery for treatment of suspected endometriosis.

  • The positive predictive value of BCL6 testing for endometriosis was 96%. This could help to identify a patient population that may require surgical treatment before embryo transfer.

  • Women with other pathologies (n = 3) also had endometrial BCL6 overexpression.
Sansone et al. (2021)

  • Age 18–42.

  • n = 10 control.

  • n = 10, stages I/II endometriosis.

  • n = 10, stages III/IV endometriosis.

  • Patients were of reproductive age, had regular menstrual cycles, without (PCOS) or hormonal birth control.

 BCL6 and SIRT1 levels were measured in serum, plasma, urine and cervical mucus using ELISA.

  • No differences in BCL6 levels were found between patients with endometriosis and controls.

  • No differences in BCL6 levels were found between Stages I/II and III/IV.

  • Levels of SIRT1 in sera were significantly elevated in women with Stages III/IV compared with controls and Stages I/II.
Shen et al. (2021)

  • Age ≤40.

  • n = 6.

  • Blood and/or endometrial samples from the mid-luteal phase of the menstrual cycle.

 Flow cytometry for endometrial B-cell subsets analysis. 1–5% of endometrial immune cells were B cells. FAS+IgD-BCL6+ GC B cells were present in the endometrium, indicating their roles in the human endometrial environment. TFH-like cells did not have a higher expression of BCL6.

BCL6, B-cell lymphoma 6; GC, germinal center; GLI1, glioma-associated oncogene homolog 1; HSCORE, a method for quantifying the staining intensity and the percentage of stained cells in IHC; IHC, immunohistochemistry; KRAS, Kirsten rat sarcoma viral oncogene homolog; qPCR, quantitative PCR; RIF, repeated implantation failure; SIRT1, Sirtuin 1; TFH, T follicular helper cells; UI, unexplained infertility; WB, western blot analysis.