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Epidemiology of Mucinous Adenocarcinomas.

ABSTRACT: Mucinous (colloid) adenocarcinomas (MAs) are a rare histological subtype of adenocarcinomas where extracellular mucin comprises more than 50% of the tumor. Most literature on MAs relate to cancers from colorectal and breast sites; however, the literature lacks a standardized overview of the MA disease entity. Particularly in colorectal cancer, some MAs may have signet ring cells floating within the mucin, which may represent a highly metastatic phenotype. MAs and signet ring cell adenocarcinomas represent a spectrum of mucin-producing neoplastic conditions where in the latter most mucin is intracellular rather than extracellular. We recently published a standardized overview of signet ring cells, and in this companion work, using a retrospective cohort approach, we summarize the clinicodemographic and mortality outcomes of MAs in sixteen primary sites, comprising 95.6% of all MAs in the Surveillance, Epidemiology, and End Results Program (SEER), a population-level cancer database covering nearly one-third of the United States population. Compared to matching nonvariant adenocarcinomas, MAs have a slightly earlier age of onset with increased rates of regional and distant disease at presentation. Survival outcomes are highly dependent on tumor location, illustrating our poor understanding of MA tumor biology. The clinical significance of MA histology depends largely on tumor site.

SUBMITTER: Benesch MGK

PROVIDER: S-EPMC7692300 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Epidemiology of Mucinous Adenocarcinomas.

Benesch Matthew G K MGK Mathieson Alexander A

Cancers 20201030 11

Mucinous (colloid) adenocarcinomas (MAs) are a rare histological subtype of adenocarcinomas where extracellular mucin comprises more than 50% of the tumor. Most literature on MAs relate to cancers from colorectal and breast sites; however, the literature lacks a standardized overview of the MA disease entity. Particularly in colorectal cancer, some MAs may have signet ring cells floating within the mucin, which may represent a highly metastatic phenotype. MAs and signet ring cell adenocarcinomas ...[more]

PMID: 33143115

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Project description:BackgroundMucinous appendiceal adenocarcinoma (MAA) is a rare, heterogeneous disease. Patients with unrespectable mucinous appendiceal adenocarcinoma presenting with peritoneal spread are treated by intraperitoneal chemotherapy, hyperthermic intraperitoneal chemotherapy, systemic chemotherapy, or targeted therapy. However, there are no guidelines for efficacious drugs against mucinous appendiceal adenocarcinoma. Therefore, relevant high-fidelity models should be investigated to identify effective drugs for individual therapy.MethodsSurgical tumor specimens were obtained from a mucinous appendiceal adenocarcinoma patient. The tissue was digested and organoid culture was established. H&E and immunohistochemistry staining as well as DNA sequencing was performed on tissue and organoid. The pathological characteristics and gene mutations of the organoid were compared to those of the original tumor. Drug sensitivity tests were performed on organoid and the patient clinical responds to chemotherapy and targeted therapy was compared.ResultsOrganoids were successfully established and stably passaged. Pathological characteristics of organoids including H&E staining and expression of protein markers (CK20, CDX-2, STAB2, CD7, PAX8) were consistent to those of the original tumor. Moreover, the organoids carried the same gene mutations as the primary tumor. Sensitivity of the organoids to chemotherapeutic drugs and tyrosine kinase inhibitors included: 5-FU (IC50 43.95 μM), Oxaliplatin (IC50 23.49 μM), SN38 (IC50 1.02 μM), Apatinib (IC50 0.10 μM), Dasatinib (IC50 2.27 μM), Docetaxel (IC50 5.26 μM), Regorafenib (IC50 18.90 μM), and Everolimus (IC50 9.20 μM). The sensitivities of organoid to these drugs were comparable to those of the patient's clinical responses.ConclusionThe mucinous appendiceal adenocarcinoma organoid model which retained the characteristics of the primary tumor was successfully established. Combined organoid-based drug screening and high throughput sequencing provided a promising way for mucinous appendiceal adenocarcinoma treatment.

Project description:BackgroundIntraoperative molecular imaging (IMI) with folate-targeted NIR tracers has been shown to improve lesion localization in more than 80% of lung adenocarcinomas. However, mucinous adenocarcinomas (MAs) and invasive mucinous adenocarcinomas (IMAs) of the lung, which are variants of adenocarcinoma, appear to have decreased fluorescence despite appropriate folate receptor expression on the tumor surface. We hypothesized that the etiology may be related to light excitation and emission through non-Newtonian fluid (mucin) produced by goblet and columnar cancer cells.MethodsIntraoperative data for 311 subjects were retrospectively reviewed from a prospectively collected 6-year database. For standardization, all patients underwent infusion of the same targeted molecular optical contrast agent (pafolacianine, folate receptor-targeted NIR fluorochrome) for lung cancer resections. Then, the ratio of the mean fluorescence intensity of the tumors and background tissues (TBR) was calculated. Tumors were examined for mucin, FRa, FRb, and immunofluorescent tracer uptake by a board-certified pathologist. The optical properties of mucin analyzed by imaging software were used to create in vitro gel models to explore the effects on NIR tracer fluorescence intensity.ResultsA large proportion (192, 62%) of the patients were female, with an average of 62.8 years and a 34-year mean pack smoking history. There were no severe (Clavien-Dindo > III) complications related to pafolacianine infusion. A total of 195 lesions in the study were adenocarcinomas, of which 19 (6.1%) were of the mucinous subtype. A total of 14/19 of the patients had a smoking history, and more than 74% of the IMA lesions were in the lower lobes. IMA lesions had a lower in situ TBR than nonmucinous adenocarcinomas (2.64 SD 0.23) vs (3.45 SD 0.11), respectively (p < 0.05). Only 9/19 (47%) were localized in situ. Tumor bisection and removal of mucin from IMAs significantly increased pafolacianine fluorescence, with resultant TBR not being significantly different from the control group (4.67 vs 4.89) (p = 0.19). Of the 16 lesions that underwent FR expression analysis, 15/16 had FR presence on cancer cells or tumor-associated macrophages in the tumor microenvironment. There was no statistically significant difference in fluorescence intensity during immunofluorescence analysis (4.99 vs 5.08) (p = 0.16). Physical removal of mucin from IMAs improved the TBR from 3.11 to 4.67 (p < 0.05). In vitro analysis of the impact of synthetic non-Newtonian fluid (agarose 0.5%) on NIR tracer fluorescence showed a decrease in MFI by a factor of 0.25 regardless of the concentration for each 5 mm thickness of mucin.ConclusionThe mucinous subtype of lung adenocarcinomas presents a unique challenge in pafolacianine-targeted IMI-guided resections. The presence of non-Newtonian fluids presents a physical barrier that dampens the excitation of the tracer and fluorescence emission detected by the camera. Knowledge of this phenomenon can allow the surgeon to critically analyze lesion fluorescence parameters during IMI-guided lung cancer resections.

Dataset Information

Epidemiology of Mucinous Adenocarcinomas.

Publications

Epidemiology of Mucinous Adenocarcinomas.

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