The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma.

OBJECTIVE: Substantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE). METHODS: Pathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI. RESULTS: 1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5-95.1), 76.8% (95% CI: 67.2-87.7) and 79.1% (95% CI: 67.6-95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS. CONCLUSIONS: Our results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women With FIGO Stage II Uterine Endometrioid Carcinoma.

OBJECTIVE: The objective of this study was to investigate the prognostic significance of the depth of cervical stromal invasion (CSI) in women with FIGO stage II uterine endometrioid adenocarcinoma (EC). METHODS: Our database of women with EC was quired for patients with stage II EC. Pathologic slides were retrieved and reviewed by gynecologic pathologists to determine cervical stromal thickness and depth of CSI as a percentage of stromal thickness (%CSI). Kaplan-Meier, univariate, and multivariate analyses were used to compare recurrence-free, disease-specific (DSS), and overall survival (OS) between women who had<50% versus ≥50% CSI. Univariate and multivariate analyses were used to assess other prognostic variables associated with survival endpoints. RESULTS: A total of 117 patients were included in our study who had hysterectomy between 1/1990 and 8/2021. Seventy-nine patients (68%) with <50% and 38 (32w%) with ≥50% CSI. After a median follow-up of 131 months, 5-year DSS was significantly worse for women with ≥50% CSI (78% vs. 91%; P =0.04). However, %CSI was not an independent predictor for any of the studied survival endpoints. Independent predictors of worse 5-year recurrence-free survival and DSS included FIGO grade 3 tumors ( P =0.02) and the presence of lymphovascular space invasion ( P =0.03). Grade 3 tumors were the only independent predictor of worse 5-year OS ( P =0.02). CONCLUSIONS: Our results suggest that deep CSI is not an independent prognostic factor for survival endpoints in women with stage II uterine endometroid adenocarcinoma. The lack of independent prognostic significance of the depth CSI needs to be validated in a multi-institutional analysis.

Clinical significance of quantitative categorization of HER2 fluorescent in situ hybridization results in invasive breast cancer patients treated with HER2-targeted agents.

HER2 (ERBB2) gene status serves as a strong predictive marker of response to HER2-targeted agents in invasive breast cancers, albeit with heterogeneous response. Our aim was to determine the distribution and prognosis of HER2 groups by fluorescent in situ hybridization (FISH) using the updated 2018 American Society of Clinical Oncology-College of American Pathologist (ASCO-CAP) guidelines. We identified 226 cases of equivocal or positive HER2 FISH invasive breast cancer (interpreted by ASCO-CAP guidelines at the time of reporting) who received HER2-targeted agents from 2006 to 2017. We subcategorized Group 1 further into three subgroups: low amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell 4.0-5.9), amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell ≥ 6), and excessive amplification (HER2/CEP17 ratio ≥ 3.0, mean HER2/cell ≥ 4.0). Outcomes studied were recurrence, metastasis, second breast primary, disease-specific survival (DSS), and overall survival (OS). Univariate analysis showed that the five categories of HER2 FISH were significantly associated with OS (p < 0.01), specifically higher HER2 amplification was associated with fewer deaths. HER2 FISH status also statistically significantly relates to DFS (p < 0.01) and metastasis (p = 0.01) but not with recurrence or second breast primary in our study. Tumor type and HER2 ISH Groups are independent predictors for both OS and DFS in our cohort. The proposed Group 1 subcategories were significantly associated with OS (p < 0.01) and DFS (p < 0.01), excessive HER2 amplification was associated with longer median survival. The Cox regression models showed better survival outcomes for the excessive amplification subgroup than the low amplified subgroup, with OS (hazard ratio = 0.63, 95% CI 0.42-0.93) and DFS (HR = 0.55, 95% CI 0.37-0.83). We demonstrated that in HER2 FISH Group 1 patients, high HER2 amplification was significantly associated with longer OS and DFS; these patients seem to benefit more from HER2-targeted regimens. We recommend reporting these Group 1 subcategories when assessing HER2 FISH.

Microvascular changes in Down syndrome with Alzheimer's-type pathology: Insights into a potential vascular mechanism for Down syndrome and Alzheimer's disease.

INTRODUCTION: The mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following amyloid ß (Aß) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer's pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. METHODS: We examined brain microvasculature in five DS subjects with AD-type histopathology, seven AD cases, and seven controls without AD-type pathology. We counted microvessels in five anatomic regions and assessed endothelial integrity by CD31 immunohistochemistry. RESULTS: Microvascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains. DISCUSSION: People with DS and trisomy 21 produce a large amount of Aß. If Alzheimer's pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Aß mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer's disease changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.