Mismatch repair deficiency is rare in bone and soft tissue tumors

INTRODUCTION: There has been an increased demand for mismatch repair (MMR) status testing in sarcoma patients after the success of immune checkpoint inhibition (ICI) in MMR deficient tumors. However, data on MMR deficiency in bone and soft tissue tumors is sparse, rendering it unclear if routine screening should be applied. Hence, we aimed to study the frequency of MMR deficiency in bone and soft tissue tumors after we were prompted by two (potential) Lynch syndrome patients developing sarcomas. METHODS: Immunohistochemical expression of MLH1, PMS2, MSH2 and MSH6 was assessed on tissue micro arrays (TMAs), and included 353 bone and 539 soft tissue tumors. Molecular data was either retrieved from reports or microsatellite instability (MSI) analysis was performed. In MLH1 negative cases, additional MLH1 promoter hypermethylation analysis followed. Furthermore, a systematic literature review on MMR deficiency in bone and soft tissue tumors was conducted. RESULTS: Eight MMR deficient tumors were identified (1%), which included four leiomyosarcoma, two rhabdomyosarcoma, one malignant peripheral nerve sheath tumor and one radiation‐associated sarcoma. Three patients were suspected for Lynch syndrome. Literature review revealed 30 MMR deficient sarcomas, of which 33% were undifferentiated/unclassifiable sarcomas. 57% of the patients were genetically predisposed. CONCLUSION: MMR deficiency is rare in bone and soft tissue tumors. Screening focusing on tumors with myogenic differentiation, undifferentiated/unclassifiable sarcomas and in patients with a genetic predisposition / co‐occurrence of other malignancies can be helpful in identifying patients potentially eligible for ICI

Measurements of the semileptonic decays (B)over-bar -> Dl(nu)over-bar and (B)over-bar -> D*l(nu)over-bar using a global fit to DXl(nu)over-bar final states

Semileptonic (B) over bar decays to DXl (nu) over bar (l = e or mu) are selected by reconstructing D(0)l and D(+)l combinations from a sample of 230 x 10(6) Y(4S) --> B (B) over bar decays recorded with the BABAR detector at the PEP-II e(+)e(-) collider at SLAC. A global fit to these samples in a three-dimensional space of kinematic variables is used to determine the branching fractions B(B- --> D(0)l (nu) over bar = (2.34 +/- 0.03 +/- 0.13)% and B(B- --> D*(0)l (nu) over bar) = (5.40 +/- 0.02 +/- 0.21)% where the errors are statistical and systematic, respectively. The fit also determines form-factor parameters in a parametrization based on heavy quark effective theory, resulting in rho(2)(D) = 1.20 +/- 0.04 +/- 0.07 for (B) over bar --> Dl (nu) over bar and rho(2)(D*) = 1.22 +/- 0.02 +/- 0.07 for (B) over bar --> D*(0)l (nu) over bar. These values are used to obtain the product of the Cabibbo-Kobayashi-Maskawa matrix element |V-cb| times the form factor at the zero recoil point for both (B) over bar --> Dl (nu) over bar decays, G(1)|V-cb| = (43.1 +/- 0.8 +/- 2.3) x 10(-3), and for (B) over bar --> D*l (nu) over bar decays, F(1)|V-cb| = (35.9) +/- 0.2 +/- 1.2) x 10(-3)