Analysis of serum HE4 levels in various histologic subtypes of epithelial ovarian cancer and other malignant tumors

BACKGROUND: The measurement of serum HE4 levels has emerged as a sensitive and specific biomarker for epithelial ovarian cancers (EOCs). However, serum levels in women diagnosed with various histologic subtypes of EOC and in women with metastatic non-ovarian primary malignancies have not been widely reported. OBJECTIVE: The goal of this study was to identify how serum HE4 levels vary in women diagnosed with different histologic subtypes of EOC and non-ovarian malignancies. METHODS: Data from six prospective pelvic mass clinical trials was combined and an evaluation of serum HE4 levels in women diagnosed with a malignancy was performed. For all patients, serum was obtained prior to surgery and final pathology, including primary tumor site, histologic subtype, grade and stage, were recorded. The mean, median, standard deviation, maximum, and minimum HE4 levels were determined for each group. RESULTS: A total of 984 patients were included in this study, with the average patient age being 60 years old. There were 230 premenopausal and 754 postmenopausal patients. Serum HE4 levels were elevated (≥70.0 pMol) in 85%of EOCs, 40%of LMP tumors, 21%of non-EOCs (germ cell tumors), 25%of cervical cancers, and 47%of non-gynecologic metastatic cancers. Analysis of histologic subtypes revealed 90%(n = 391) of serous, 85%(n = 73) of endometrioid, 45%(n = 42) of mucinous, 86%(n = 51) of mixed tumors, and 69%(n = 36) of clear cell tumors had elevated serum HE4 levels. CONCLUSIONS: Serum HE4 levels are most often elevated in women with high grade serous and endometrioid EOCs, and though serum elevations are seen more often with advanced stage disease, HE4 is also often elevated in early stage disease and lower grade tumors.

The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics

Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.

Borderline ovarian tumor frozen section diagnoses with features suspicious of invasive cancer: a retrospective study

Background A frozen section diagnosis of a borderline ovarian tumor with suspicious features of invasive carcinoma (“at least borderline” or synonymous descriptions) presents us with the dilemma of whether or not to perform a full ovarian cancer staging procedure. Quantification of this dilemma may help us with the issue of this clinical decision. The present study assessed and compared both the prevalence of straightforward borderline and “at least borderline” frozen section diagnoses and the proportion of these women with a final histopathological diagnosis of invasive carcinoma, with a special interest in histologic subtypes. Methods A retrospective cohort study was performed in three hospitals in The Netherlands. All women that underwent ovarian surgery with perioperative frozen section evaluation in one of these hospitals between January 2007 and July 2018 were identified and included in case of a borderline or “at least borderline” frozen section diagnosis and a borderline ovarian tumor or invasive carcinoma as a final diagnosis. Results A total of 223 women were included, of which 41 women (18.4%) were diagnosed with “at least borderline” at frozen section. Thirteen of forty-one women (31.7%) following “at least borderline” frozen section diagnosis and 14 of 182 women (7.7%) following a straightforward borderline frozen section diagnosis were diagnosed with invasive carcinoma at paraffin section evaluation (p < 0.001). When compared to straightforward borderline frozen section diagnoses, the proportion of women diagnosed with invasive carcinoma increased from 3.1 to 35.7% for serous tumors (p = 0.001), 10.0 to 21.7% for mucinous tumors (p = 0.129) and 50.0 to 75.0% (p = 0.452) in case of other histologic subtypes following an “at least borderline” frozen section diagnosis. Conclusions Overall, when compared to women with a decisive borderline frozen section diagnosis, women diagnosed with “at least borderline” frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis (7.7% vs 31.7%). Especially in the serous subtype, full staging during initial surgery might be considered after preoperative consent to prevent a second surgical procedure or chemotherapy in unstaged women. Further studies are needed to evaluate whether additional sampling in case of an “at least borderline” diagnosis may decrease the risk of surgical over-treatment.

The Prognostic Impact of Histology in Esophageal and Esophago-Gastric Junction Adenocarcinoma

Stage significantly affects survival of esophageal and esophago-gastric junction adenocarcinomas (EA/EGJAs), however, limited evidence for the prognostic role of histologic subtypes is available. The aim of the study was to describe a morphologic approach to EA/EGJAs and assess its discriminating prognostic power. Histologic slides from 299 neoadjuvant treatment-naïve EA/EGJAs, resected in five European Centers, were retrospectively reviewed. Morphologic features were re-assessed and correlated with survival. In glandular adenocarcinomas (240/299 cases—80%), WHO grade and tumors with a poorly differentiated component ≥6% were the most discriminant factors for survival (both p < 0.0001), distinguishing glandular well-differentiated from poorly differentiated adenocarcinomas. Two prognostically different histologic groups were identified: the lower risk group, comprising glandular well-differentiated (34.4%) and rare variants, such as mucinous muconodular carcinoma (2.7%) and diffuse desmoplastic carcinoma (1.7%), versus the higher risk group, comprising the glandular poorly differentiated subtype (45.8%), including invasive mucinous carcinoma (5.7%), diffuse anaplastic carcinoma (3%), mixed carcinoma (6.7%) (CSS p < 0.0001, DFS p = 0.001). Stage (p < 0.0001), histologic groups (p = 0.001), age >72 years (p = 0.008), and vascular invasion (p = 0.015) were prognostically significant in the multivariate analysis. The combined evaluation of stage/histologic group identified 5-year cancer-specific survival ranging from 87.6% (stage II, lower risk) to 14% (stage IVA, higher risk). Detailed characterization of histologic subtypes contributes to EA/EGJA prognostic prediction.

Sarcomas: New Biomarkers and Therapeutic Strategies

Bone and soft tissue sarcoma (STS) are heterogeneous diseases comprised of various molecular and histologic subtypes [...]

651 A META-ANALYSIS OF SURVIVAL AFTER NEOADJUVANT CHEMORADIOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY IN RESECTABLE LOCALLY ADVANCED ESOPHAGEAL CANCERS BASED ON HISTOLOGIC SUBTYPES

Neoadjuvant treatments provided survival benefits over surgery alone in resectable locally advanced esophageal and esophagogastric junction (EGJ) cancer patients. Both neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) are shown to be effective treatments. However, the direct comparison between two methods based on histologic subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC) is still limited. This study examined the hypothesis that nCRT could provide the better overall survival (OS) than nCT. Methods A comprehensive search of studies comparing nCRT and nCT in patients with esophageal and EGJ cancer based on histologic subtypes was conducted. A meta-analysis of randomized (8 articles) and non-randomized (15 articles) studies was performed using odds ratio (OR) and 95% confidence intervals (CI95%). The OS was the main objective, whereas the secondary objective were complete pathological response (pCR) rate, curative resection (R0) rate, locoregional progression free-survival (L-PFS) rate, postoperative complications and mortality. Results Twenty three articles included 1,671 SCC and 9,285 AC patients. Neither 3- nor 5-year OS was found to be different. However, SCC patients receiving nCRT showed the better 3-year OS (OR 1.67, CI95% 1.17–2.40, p = 0.005). Both pCR and R0 rates were superior in nCRT group (OR 3.30, CI95% 2.46–4.44 and 2.46, CI95% 1.66–3.65, p &lt; 0.00001, respectively). The better 3-year L-PFS was observed in nCRT group (OR 1.47, CI95% 1.17–1.85, p = 0.008), but 5-year L-PFS was comparable. The 30-day mortality was comparable, while 90-day mortality was higher in nCRT group (OR 1.32, CI95% 1.01–1.72, p = 0.04). Conclusion The nCRT provided the better overall survival especially in SCC patients and also increased locoregional control. Meanwhile, postoperative complications and mortality were higher after nCRT. Due to clinical heterogeneity, the multidisciplinary team management for each patient is required before treatment.