One mutation in gene PTCH1 (Protein patched homolog 1) and two acquired anti-PD1 candidate resistance mutations of gene B2M (β2 microglobulin) were identified in association with distant metastasis.
Tumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections.
In contrast, when the molecular mechanism of the tumor MHC-I loss is irreversible ("hard") due to a genetic defect in the gene/s coding for MHC-I heavy chains (chromosome 6) or beta-2-microglobulin (B2M) (chromosome 15), malignant cells are unable to upregulate MHC-I, remain undetectable by cytotoxic T-cells, and continue to grow and metastasize.
Genome profiling by SNP arrays revealed that HLA class I loss in both metastases originated from a shared chromosome 15q alteration and independently acquired focal B2M gene deletions.
In this study, we investigated a possible mechanism of β2-microglobulin (β2M) function in cancer metastases in vitro, using a human ovarian carcinoma cell line.
Our data show for the first time that absence of B2M protein expression identifies MMR-deficient cancers with a favourable clinical course and absence of metastatic disease.
Using the mean of the 15 genes as an internal reference control, we observed that low expression of beta(2)microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC)=0.85; 95% confidence interval (CI)=0.69-0.94).
Overexpression of beta2-microglobulin is associated with poor survival in patients with oral cavity squamous cell carcinoma and contributes to oral cancer cell migration and invasion.