FDA Approves Pembrolizumab for Microsatellite Instability-High and Mismatch Repair Deficient Cancers

[D.ap]

"The FDA has granted an accelerated approval to pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed after prior treatment and who have no satisfactory alternative treatment options, as well as for patients with MSI-H or dMMR colorectal cancer following progression on a fluoropyrimidine, oxaliplatin, and irinotecan. "



http://www.onclive.com/web-exclusives/f ... nt-cancers

[Olga]

We should try to find a more exact list of the cancers that are incl. in the Microsatellite Instability-High and Mismatch Repair Deficient Cancers...As I understand sarcomas should be there too but I am not sure as how are the insurance companies reading it.

[D.ap]

Here's one , Olga

Microsatellite Instability in Gynecological Sarcomas and in hMSH2 Mutant Uterine Sarcoma Cell Lines Defective in Mismatch Repair Activity


http://cancerres.aacrjournals.org/conte ... 5664.short

[D.ap]

"Mismatch repair protein expression and microsatellite instability: a comparison of clear cell sarcoma of soft parts and metastatic melanoma"

Abstract
Clear cell sarcoma of soft parts is a rare soft tissue malignancy that shows phenotypic overlap with cutaneous melanoma but can be distinguished by the presence of a t(12;22) translocation. Microsatellite instability (MSI), a variation in the lengths of short repeat DNA segments in the genome, has been implicated in melanoma tumorigenesis, but is rare or absent in clear cell sarcoma. Defects in the mismatch repair (MMR) enzyme complex correlate with MSI in some tumor types, allowing the use of immunohistochemistry for the MMR proteins hMLH1 and hMSH2 to predict the presence of MSI. To determine if the association between MMR defects and MSI extends to clear cell sarcoma, we compared a group of nine clear cell sarcomas to 11 metastatic melanomas on the basis of MSI and the expression of MMR proteins. MSI was studied using fluorescence-based multiplexed PCR of five loci. Immunohistochemistry was evaluated on formalin-fixed paraffin-embedded tissue for hMLH1, hMHS2 and hMSH6. MSI was present in only 1/9 (11%) clear cell sarcoma case and in 8/11 (73%) melanoma cases. Immunostaining for hMLH1 and hMSH2 was preserved in all the clear cell sarcomas but loss of immunostaining for one or both proteins was seen in 6/11 melanomas (55%). hMSH6 was detected in 7/9 (78%) clear cell sarcomas and 10/11 (91%) of melanomas. Clear cell sarcoma and metastatic melanoma differed significantly with respect to the presence of MSI (P=0.010) and staining for hMLH1 and/or hMSH2 (P=0.014) but not hMSH6 (P=0.57). Mismatch repair, and consequently genomic instability may contribute to tumorigenesis in melanoma but not clear cell sarcoma. Immunostaining for hMLH1 and hMSH2 and MSI analysis may be helpful in the differential diagnosis of large soft tissue or visceral malignancies



http://www.nature.com/modpathol/journal ... 0611a.html

[D.ap]

The sameness of microsatellite instability and mismatched repair


https://www.ncbi.nlm.nih.gov/m/pubmed/15749237/

In visiting with various people , it appears that the useage definition and or application / prerequisite of having
MSI-H, or simple MSI presense , could be eventually applicable to Asps?

It's been said that MSI-H has been shown to respond to anti PD1 meds , but it's not known if because antipd1 works is because of the presence of more PDL-1? Not known if MSI and PDL1 corellate and are synomist . Are the same ?

I'm going to send the article to Joshua's oncologist and see what he says . We see him later this week for our 22nd Opdivo infusion .