Table 2 Likelihood ratio analysis for the evaluation of ovarian cancer histological subtypes in association with BRCA1 and BRCA2 pathogenic variant status.

From: Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2

 

BRCA1 carriers

BRCA2 carriers

Non-carriers

Total

Histological subtypes

N (%)

LR (95% CI)

ACMG/AMP strength

N (%)

LR (95% CI)

ACMG/AMP strength

N (%)

N (%)

HGSC

1578 (77.2)

1.13 (1.10–1.16)

Non-informative

597 (78.4)

1.15 (1.10–1.19)

Non-informative

5183 (68.5)

7358 (70.9)

LGSC

58 (2.8)

0.50 (0.38–0.66)

Non-informative

23 (3.0)

0.53 (0.35–0.81)

Non-informative

429 (5.7)

510 (4.9)

Mucinous

21 (1.0)

0.24 (0.15–0.37)

Supporting Benign

14 (1.8)

0.43 (0.25–0.73)

Supporting Benign

325 (4.3)

360 (3.5)

Endometrioid

226 (11.1)

1.17 (1.02–1.35)

Non-informative

65 (8.5)

0.91 (0.71–1.16)

Non-informative

713 (9.4)

1004 (9.7)

Clear cell

38 (1.9)

0.23 (0.17–0.32)

Supporting Benign

15 (2.0)

0.25 (0.15–0.41)

Supporting Benign

605 (8.0)

658 (6.3)

‘Other’

123 (6.0)

1.45 (1.19–1.78)

Non-informative

47 (6.2)

1.49 (1.11–2.01)

Non-informative

313 (4.1)

483 (4.7)

 

2044

  

761

  

7568

10,373

  1. N number of data points, LR likelihood ratio, CI confidence interval, ACMG/AMP American College of Medical Genetics/Association for Molecular Pathology, HGSC high-grade serous carcinomas, LGSC low-grade serous carcinomas
  2. The analysis was based on 10,373 cases, including 2044 BRCA1 carriers, 761 BRCA2 carriers and 7568 non-carriers. In brackets, the histotype frequency for each group is provided. The ‘other’ category denominates rare forms of ovarian cancer not belonging to any of the other subtypes, including tumours defined as: ‘other’ by data sources not specifying tumour histology; mixed-epithelial; carcinosarcomas; transitional cell (Brenner tumours); undifferentiated or poorly differentiated; squamous cell. LR > 1: Histotype association with pathogenic variant, Pathogenic evidence; LR < 1: Prediction of non-carrier for pathogenic variant, Benign evidence. Evidence strength was measured based on Bayesian modelling of ACMG/AMP rules (see 'Materials and methods'); Supporting Benign (LR ≥ 0.23–0.48), Moderate Benign (LR ≥ 0.053–0.23), Supporting Pathogenic (LR ≥ 2.08–4.30), non-informative (0.48 ≤ LR ≤ 2.08). LR estimates reaching informative ACMG/AMP strengths at a statistically significant CI (i.e., not spanning 1), are highlighted in bold.
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