METHODS: This was a multicenter, cross-sectional prevalence study on PD-L1 positivity among patients with advanced-stage TNBC in Malaysia. Patients were identified using medical records and were enrolled in the study if they met the inclusion criteria. PD-L1 evaluation was performed using archived formalin-fixed paraffin-embedded tissue specimens. Demographic and clinical data were also obtained and summarized using descriptive statistics. The association of these parameters with PD-L1 positivity was assessed using chi-square and logistic regression analysis.
RESULTS: Three medical centers provided 138 complete cases for analysis. Of these 138 cases, 52 (37.7%; 95% confidence interval, 29.6%-46.3%) showed positive PD-L1 expression, defined as immune cell PD-L1 expression ≥ 1%. In a univariate analysis, stage III of the disease and tumor samples from resected specimens were significantly associated with a positive PD-L1 status. However, further assessment using a multivariate model revealed that only resected tumor samples remained significantly associated with PD-L1 positivity after controlling for disease staging.
CONCLUSION: The prevalence of PD-L1 positivity among patients with stage III or IV TNBC was 37.7%. A significant association was noted between PD-L1 positivity and the tumor tissue obtained from resected specimens. Although the mechanism and clinical significance of this association remain unclear, this finding indicates a possible disparity in the PD-L1 status of samples obtained using surgical resection or biopsy.
Methods: Five key themes were reviewed using existing literature (role of leadership; education, training, and continuing professional development; technology; accreditation, management, and quality standards; and reimbursement systems). A tiered system is described, building on existing proposals. The economic analysis draws on the very limited published studies, combined with expert opinion.
Results: Countries have underinvested in pathology services, with detrimental effects on health care. The equipment needs for a tier 1 laboratory in a primary health facility are modest ($2-$5,000), compared with $150,000 to $200,000 in a district hospital, and higher in a referral hospital (depending on tests undertaken). Access to a national (or regional) specialized laboratory undertaking disease surveillance and registry is important. Recurrent costs of appropriate laboratories in district and referral hospitals are around 6% of the hospital budget in midsized hospitals and likely decline in the largest hospitals. Primary health facilities rely largely on single-use tests.
Conclusions: Pathology is an essential component of good universal health care.
METHODS: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining.
RESULTS: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation (P = .026), cytokeratin 5/6 positivity (P = .028), and IGFBP2 expression (P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity (P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant.
CONCLUSIONS: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression.