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/Objective Women with female reproductive system involvement by GISTs have an unfavorable outcome. We explored the possibility that the more aggressive behavior of GYN-GIST is related to a specific genetic alteration. Our objective was to study such tumors in a cohort of women in search of actionable genes for evolving targeted therapy. Methods/Case Report The pathology databases (2004-2020) of the participating institutions were searched for GIST with histologically proven GYN-GIST (study group). The control group consisted of women known to have high risk GIST without genital tract involvement. Patients for whom genetic testing of their GISTs and follow-up information were available were included in the study. Results (if a Case Study enter NA) Of 1082 patients with GIST, eight patients fulfilled the study group criteria. Primary sites for both groups were as follows: 5 small bowel, 1 colon, 1 rectum, 1 stomach. The mean follow-up period was 86 and 77 months (study and control, respectively, p=0.34). Favorable outcomes (disease free, stable disease) were seen in 2 and 5 women (study and Control, respectively). Unfavorable outcomes (death, progression on treatment) were seen in 6 and 3 women (study and control, respectively, p&amp;lt;0.05). All patients had initial KIT mutation (exons 11 or 9). In addition, 4 patients from the study group (of 5 tested) had alteration in TP53. One patient without TP53 alterations is disease free. None of the neoplasms from 8 patients tested in the control group had TP53 alterations; fatal outcomes in this group were related to superimposed KIT exon 17 mutation. Conclusion Alterations in TP53 (linked to the poor outcome in a host of tumors) may be related to adverse outcome in patients GYN-GIST patients and may be a potential focus as targeted therapy evolves in those patients.

Aggressive Behavior of Gastrointestinal Stromal Tumors (GISTs) Involving the Female Genital Tract (GYN- GIST) is Associated with TP53 Alterations