ARID1A is a recently identified tumor suppressor gene that is mutated in approximately 50% of ovarian clear cell and 30% of ovarian endometrioid carcinomas. The mutation is associated with loss of protein expression as assessed by immunohistochemistry. In this study, we evaluated ARID1A immunoreactivity in a wide variety of carcinomas in order to determine the prevalence of ARID1A inactivation in carcinomas; mutational analysis of ARID1A was performed in selected cases. Immunoreactivity was not detected (corresponding to inactivation or mutation of ARID1A) in 36 (3.6%) of 995 tumors. Uterine low-grade endometrioid carcinomas demonstrated a relatively high frequency of loss of ARID1A expression, as 15 (26%) of 58 cases were negative. The other tumor that had a relatively high frequency loss of ARID1A expression was gastric carcinoma (11%). Mutational analysis showed 10 (40%) of 25 uterine endometrioid carcinoma, none of 12 uterine serous carcinomas and none of 56 ovarian serous and mucinous carcinomas harbored somatic ARID1A mutations. All mutations in endometrioid carcinomas were nonsense or insertion/ deletion mutations and tumors with ARID1A mutations demonstrated complete loss or clonal loss of ARID1A expression. In conclusion, this study is the first large-scale analysis of a wide variety of carcinomas showing that uterine low-grade endometrioid carcinoma is the predominant tumor type harboring ARID1A mutations and frequent loss of ARID1A expression. These findings suggest that the molecular pathogenesis of low-grade uterine endometrioid carcinoma is similar to that of ovarian low-grade endometrioid and clear cell carcinoma, tumors that have previously been shown to have a high frequency of loss of expression and mutation of ARID1A.

Exome sequencing of ovarian clear-cell carcinoma has identified somatic mutations in PPP2R1A, a subunit of protein phosphatase 2A. The present study was performed to determine the frequency of PPP2R1A mutations in exon 5, which harbors previously reported mutation hot spots, and adjacent exon 6, in 209 ovarian and 56 uterine tumors of various histologic subtypes. PPP2R1A mutations were demonstrated in 10 of 110 type I ovarian tumors (9.1%) including low-grade serous, low-grade endometrioid, clear-cell, and mucinous carcinomas. In contrast, none of 71 type II ovarian (highgrade serous) carcinomas exhibited PPP2R1A mutations. Moreover, PPP2R1A mutations were observed in 2 of 30 type I uterine (endometrioid) carcinomas (6.7%) and 5 of 26 type II uterine (serous) carcinomas (19.2%). Of the 18 mutations, 13 affected the R182 or 183, and there were 5 novel mutations including 3 involving S256, 1 involving W257, and 1 involving P179. All mutations were located in the ␣-helix repeats near the interface between the A subunit and the regulatory B subunit of the enzyme complex. These data provide new evidence that PPP2R1A somatic mutations occur in certain types of uterine and ovarian neoplastic lesions, especially uterine serous carcinomas, and suggest that mutation of PPP2R1A may participate in the pathogenesis of ovarian type I and uterine type II carcinomas. A recent genome-wide sequencing analysis of all exons from ovarian clear cell carcinomas led to the discovery of somatic missense mutations in PPP2R1A in approximately 7% of these tumors.1 PPP2R1A encodes a constant regulatory subunit of the protein phosphatase 2A holoenzyme, which is one of four major serinethreonine phosphatases.2 Protein phosphatase 2A is composed primarily of a catalytic C subunit and a scaffolding subunit A (PPP2R1A and PPP2R1B) and a regulatory subunit B. Protein phosphatase 2A can be regulated by binding of at least 18 different regulatory B subunits to the core enzyme. The regulatory B subunit has been implicated in controlling the substrate specificity, cellular localization and enzymatic activity of protein phosphatase 2A, which participates in negative regulation of cellular proliferation among several other cellular functions.2,3 Moreover, the regulatory subunit competes with virus-producing proteins including the small T antigens of the papovaviruses SV40 and polyoma, and the middle T antigen of polyoma, 4 which suggests that protein phosphatase 2A has a role in the pathogenesis of virus-associated tumors.Uterine carcinomas can be classified as type I or type II, and develop along unique molecular pathways. Type I uterine tumors are composed of endometrioid carcinomas, which frequently harbor mutations in CTNNB1, PTEN, ARID1A (BAF250A), and PIK3CA, whereas type II tumors are composed of serous carcinomas, which contain TP53 mutations in most cases. 5 Patients with type I tumors are typically younger, and carcinoma develops at an earlier stage and has a more indolent clinical course than in patients with type II tumors. Type I uterine c...

Among our cohort with acute poststroke aphasia, the PACSLAC-II was not able to overall differentiate patients experiencing experimental mechanical pain, although differences in those experiencing the strongest pain stimulus were significant. The detection of pain-specific facial activation and negative valence in the placebo group indicates that pain and distress are unmet needs among stroke patients who are unable to verbally communicate.

Moderate-to-severe GCA is most likely to occur in the presence of AD or CVD and should not be solely attributed to age when evaluating clinical imaging findings in the workup of cognitive complaints. Developing optimal diagnostic and treatment strategies for cognitive decline in the setting of GCA requires an understanding of its risk factors in the aging population.

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