Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

The dilemmas of the liberal welfare state, 1945--1964: Gender, race, and Aid to Dependent Children.

This dissertation argues that Aid to Dependent Children---the federal welfare program for needy women and children---was dramatically reformed in the twenty years after World War II. The reform grew out of a postwar movement for rehabilitating welfare clients among a coalition of liberal organizations including foundations, universities, interest groups, and welfare and social work organizations. Rather than remaining an income support program for needy single mothers and their children, ADC was redefined as a social services program which rehabilitated welfare clients to independence, largely by encouraging clients to work. This dissertation also argues that welfare reform was intertwined with larger national political issues in postwar America. Welfare reformers saw rehabilitation as a way to inject efficiency and specialized knowledge into welfare, a program which policy expertise had long by-passed. More importantly, reformers' interest in women, welfare, and work reflected broader social issues of the period, including the rediscovery of poverty, changing family structure, and women's economic roles. Above all, welfare reformers, like other liberals, had faith in the ability of the postwar affluent society to solve the social problems associated with welfare. Finally, this dissertation argues that the fate of postwar welfare reform reflected the central dilemma facing the liberal welfare state after World War II---how to address gender and race in social policy. Because rehabilitative welfare reform addressed a target population disdained or overlooked by many Americans---poor African-American and white women---it comprised a unique approach to solving poverty among liberals. The goals of rehabilitating poor women initially generated a political consensus, reflected in successful federal legislation in 1956 and 1962. But this consensus soon deteriorated. Political opposition to welfare among conservatives exploded in 1960, and challenged the legitimacy of liberal welfare reform. More importantly, in the early 1960s, new liberal policy activists in civil rights, women's issues, and poverty trumped welfare reformers' exclusive claims to helping poor African-American and white women, pushing rehabilitation---and its target population of welfare clients---to the fringes of the liberal social agenda, and fracturing the liberal social agenda.Ph.D.American historySocial SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/132845/2/9990945.pd