Mucinous Colorectal Adenocarcinomas Research Articles

Abstract 18: Transcriptomic analysis of mucinous adenocarcinoma in genetically-engineered mouse model

Abstract Background and Aim: The nature and characteristic of human mucinous colorectal adenocarcinomas have not been well elucidated yet. We previously reported a genetically-engineered mouse model for colonic neoplasia producing mucin based on inactivation of Transforming Growth Factor β Receptor Type II (Tgfbr2) and Apc (CDX2P-G19Cre;Apc flox/+;Tgfbr2flox/flox), which is useful to investigate the mechanism of tumor formation. This mouse model developed colonic neoplasia from 12 weeks of age. Despite the same genotype, 40% of the tumors were found mucinous adenocarcinoma and 28% were high-grade adenoma. For further investigation, we herein perform transcriptomic analysis to clarify the molecular differences in these two histologically different tumors. Method: Total RNA were extracted from mucinous adenocarcinomas and high-grade adenomas in CDX2P-G19Cre;Apcflox/+;Tgfbr2 flox/flox mice from fresh frozen tumors (n=3, each). Then, RNA-seq and Gene Set Enrichment Analysis were performed. Samples were sequenced on NovaSeq 6000, and gene sets queried included the Hallmark. Results: Mucinous adenocarcinoma and high-grade dysplasia were differentially clustered in principal component analysis despite the same genotype. Gene set enrichment analysis showed 19 upregulated signaling pathways including KRAS signaling and epithelial mesenchymal transition, and 8 suppressed signaling pathways including E2F targets and MYC targets in mucinous adenocarcinoma compared to high-grade dysplasia (FDR < 0.05). Conclusions: By comparing transcriptome of mucinous adenocarcinoma with high-grade adenoma in our mouse model, 27 differential signal pathways were detected. Some of these pathways are presumably associated with the nature and the characteristics of mucinous adenocarcinoma. We are further investigating the effects of these differences in signal pathways and the correlation with human mucinous adenocarcinoma. Citation Format: Haruki Sada, Hiroaki Niitsu, Hikaru Nakahara, Masashi Miguchi, Naoya Sakamoto, Naohide Oue, Hirotaka Tashiro, Hideki Ohdan, Takao Hinoi. Transcriptomic analysis of mucinous adenocarcinoma in genetically-engineered mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 18.

Bilateral blockade of MEK- and PI3K-mediated pathways downstream of mutant KRAS as a treatment approach for peritoneal mucinous malignancies.

Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo. By knockdown of mutant KRAS we show that, mutant KRAS (a) is necessary for MUC2 production in vitro and (b) synergistically engages PI3K/AKT and MEK/ERK pathways to maintain MUC2 expression in MCA cells. These results define a novel and a previously undescribed role for oncogenic KRAS in mucinous cancers. MCA cells were sensitive to MEK inhibition suggesting cellular dependence (‘addiction’) of KRAS-mutant MCA cells on hyperactivation of the MEK-driven pathway. Interestingly, MCA cells, though initially sensitive, were later resistant to PI3K single agent inhibition. Our studies suggest that this resistance involves dynamic rewiring of signaling circuits mediated through relief of RTK inhibition and MEK-ERK rebound activation. This resistance however, could be overcome by co-targeting of PI3K and MEK. Our studies thus provide a rational basis for MEK- and PI3K-targeted combination therapy for not only KRAS mutant MCA but also for other related mucinous neoplasms that overproduce MUC2 and have a high rate of KRAS mutations such as pseudomyxoma peritonei.

Predictors of lymph node metastasis and prognosis in early colorectal cancer patients with signet-ring cell and mucinous adenocarcinomas.

717 Background: The local excision of early colorectal cancer is limited by the presence of lymph node metastasis. Signet-ring cell carcinomas and mucinous adenocarcinomas are two relatively infrequent histological subtypes. However, little is known about the predictors of lymph node metastases and prognosis to support the feasibility of local excision in early-stage signet-ring cell and mucinous colorectal adenocarcinomas. Methods: The Surveillance Epidemiology and End Results Database (1988 to 2006) from the National Cancer Institute was used to identify all patients with T1 adenocarcinomas, including conventional adenocarcinoma (AC), mucinous adenocarcinomas (MAC), and signet-ring cell carcinoma (SRC). The prevalence of lymph node metastasis was assessed, and the long-term survival rate in the above three types of colorectal cancer was calculated. Results: Final cohorts of 47,260 patients were eligible for analysis. SRC accounted for 0.3% and MAC accounted for 3.7% of the entire cohort of colorectal adenocarcinomas. Compared to AC, SRC and MAC more frequently presented at a younger age, were located in the proximal colon, and exhibited a higher grade. The incidence of lymph node metastasis in AC, MAC, and SRC was 5.8%, 10.8%, and 15.3%, respectively. Patients with SRC were associated with a worse prognosis, regardless of the tumor location. Patients with MAC of the rectum, but not the colon, were associated with a reduced implication of prognosis. After adjusting for other clinicopathological factors, SRC and MAC of the rectum were independently associated with a high risk of death (HR 2.70, CI 1.77-4.12 and HR 1.65, CI 1.38-1.98 for SRC and MAC, respectively). Histology was not found to be an independent prognostic factor in patients with colon cancer. Conclusions: MAC and SRC are two distinct subtypes of colorectal cancer that require special attention despite their relatively rare prevalence. T1 patients with SRC and patients with MAC of the rectum have higher incidences of lymph node metastasis (LNM), and with these adverse outcomes, local excision is not recommended. Although MAC of the colon has a high rate of LNM, the prognosis of this type is similar to that of AC.

Abstract 2661: Bilateral blockade of MEK- and PI3K-driven pathways is effective in the treatment of KAS mutant mucinous colorectal cancer cells

Abstract Purpose. A significant proportion of sporadic colorectal cancers (CRCs) (10-15%) are of the mucinous subtype (>50% of the tumor). Mucinous colorectal adenocarcinomas (MCAs) are clinically, morphologically and molecularly distinct from nonmucinous CRCs as they show a different spectrum of genetic alterations (higher KRAS mutations, MSI-H, lower p53, high MUC2) and exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement). MCAs are associated with poorer response to chemotherapy and have limited treatment options. The purpose of this study was to test the effectiveness of combinatorial targeting of two KRAS-associated parallel pathways in an attempt to counter adaptive resistance associated with single pathway inhibition. Methods. Two KRAS mutant MCA cell lines LS174T and RW7213 were treated with two small molecule inhibitors, GDC0973 and GDC0941, to block mitogen-activated extracellular regulated kinase kinase (MEK) and phosphoinositide 3-kinase (PI3K) respectively. Adaptive resistance of these two cell lines to the PI3K inhibitor (PI3Ki) was examined by protein phospho-receptor tyrosine kinase (RTK) arrays, western blots and immunocytochemistry. Results. Bioinformatic analysis of the colon cancer datasets in the cancer genome atlas (TCGA) showed increased mutation rates in mucinous over nonmucinous CRCs for effectors of RAS-RAF-MEK-ERK (80% versus 41.9%) and PI3K-AKT-mTOR (60% versus 21.8%) pathways. Both MCA cell lines were sensitive to MEK inhibitor (MEKi) treatment. In contrast, these cell lines, though initially sensitive to PI3Ki, later became resistant. Concomitant with the development of resistance were a) increase in phosphorylated RTKs including IR, IGF-1R, EGFR, ErbB2 b) increase in phosphorylated ERK and AKT, c) nuclear translocation of the transcription factor FOXO3A and d) a decrease in proapoptotic protein BIM. Combinatorial treatment of PI3Ki and MEKi synergistically reduced viability of MCA tumor cells with attendant decrease in phosphorylated ERK and AKT and increase in BIM. Conclusions. Our data suggest cellular dependence (‘addiction’) of KRAS-mutant mucinous CRC cells on hyperactivation of MEK and PI3K pathways. Interestingly, PI3K single agent inhibition initially triggers pathway downregulation and reduced tumor cell viability but later leads to development of adaptive resistance. Our studies suggest this resistance involves dynamic rewiring of signaling circuits mediated through FOXO3A nuclear localization, relief of RTK inhibition, MEK-ERK activation and BIM reduction. Adaptive resistance however, can be overcome by co-targeting of PI3K and MEK. Our studies thus provide a rational basis for MEKi and PI3Ki combination therapy for KRAS mutant CRCs. Citation Format: Murali R. Kuracha, Peter Thomas, Brian W. Loggie, Venkatesh Govindarajan. Bilateral blockade of MEK- and PI3K-driven pathways is effective in the treatment of KAS mutant mucinous colorectal cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2661. doi:10.1158/1538-7445.AM2015-2661

529 The Cancer Research UK Stratified Medicine Programme: From national screening to national trial

Background: The increasing demand for analysis of multiple predictive genetic markers in tumour samples to guide therapeutic decision-making requires the rapid validation and uptake of new knowledge and technology, as well as collaboration between clinical teams, cellular pathology and molecular genetics laboratories. Material and Methods: Between 2011 and 2013, formalin-fixed paraffinembedded tumour samples from patients consented through a network of hospitals underwent targeted mutation analysis. This was initially performed using Sanger sequencing and similar methods but following cross-validation an amplicon-based targeted next generation sequencing panel was implemented. Clinical information based on the requirements of the national cancer registration dataset was also centrally collated for each participant. The current second phase of the initiative has a sole focus on patients with advanced lung cancer, and aims to expand the geographical reach to perform molecular pre-screening of samples to help determine patient eligibility for the National Lung Matrix Trial, a multi-arm stratified phase II clinical trial of novel therapeutics. Results: 10,754 patients (98% of those approached) consented to analysis of material during phase one, with 9010 samples submitted for analysis. The table shows the overall results of analysis for the first 7850 samples. Analysis by histological subtype enriches for certain mutations, with 925 pulmonary adenocarcinomas showing 36.5% KRAS mutations, 11.6% EGFR mutations and 2.5% ALK gene rearrangements and 56 mucinous colorectal adenocarcinomas showing 43.5% BRAF mutations and 50% KRAS mutations. Conclusions: A centralised national testing network for genetic analysis of formalin-fixed paraffin-embedded tumour samples is feasible and acceptable to patients and clinicians, with applications beyond genotyping for currently licensed oncologic therapies. Acknowledgements: Funding for the Stratified Medicine Programme is acknowledged from Cancer Research UK and programme founding partners AstraZeneca and Pfizer.

Prior appendectomy does not protect against subsequent development of malignant or borderline mucinous ovarian neoplasms

BackgroundDue to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. MethodsThe New England Case–Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. ResultsFrom the New England Case–Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83–1.92, p=0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48–2.80, p<0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20−/MUC2−/CDX2−, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7−/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. ConclusionPrior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases. FundingNational Cancer Institute grants P50-CA105009 and R21 CA-156021; The Honorable Tina Brozman ‘Tina's Wish’ Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Dana-Farber Cancer Institute — Susan Smith Center for Women's Cancers; Robert and Deborah First Fund; The Gamel Family Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Arthur Sachs/Fulbright/Harvard; La Fondation Philippe; La Fondation de France.

Abstract A11: Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors

Abstract Background: Mucinous ovarian tumors (MOT) have been linked to mucinous colorectal and appendiceal adenocarcinomas. However, recent molecular studies suggest MOT may share more in common with pancreatic mucinous cystic neoplasms (MCN). Commonalities between these seemingly disparate tumors are explored. Methods: Epidemiologic features of MOT and mucinous gastrointestinal tumors were compared using the SEER database. Regional cases of 287 mucinous ovarian tumors were examined against 2,339 age-matched controls to delineate MOT risk factors. A case series of MCN was identified by chart review. Protein expression patterns among tumors were examined using seven immunohistochemical markers. Results: SEER revealed that among GI neoplasms the epidemiology of MCN was most similar to MOT by age, race, and stage. MCN occurred almost exclusively in women, with a sex ratio of 19:1, compared to 1•1:1 and 1•2:1 for mucinous colorectal and appendiceal adenocarcinomas. In the case-control study, appendectomy and cervical conization did not reduce the risk of MOT, while smoking (OR 2•68, 95% CI 1•85-3•89, p&amp;lt;0•001), was associated with an increased risk of MOT. Smoking was similarly common among MCN patients. Histologically, MOT and MCN were CK7+, CK20-, MUC2-, and CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were CK7-, CK20+, MUC2+, and CDX2+. Interpretation: Clinical and morphologic similarities between MOT and MCN suggest a common pathogenesis, potentially a shared precursor such as embryologic rests that stopped in the pancreatic buds during migration of the primordial follicles to the gonads during development. This implies mucinous ovarian tumors may originate from primordial follicles, not the ovarian surface epithelium, offering a novel explanation for their pathogenesis. Citation Format: Intidhar Labidi-Galy, Kevin M. Elias, Allison F. Vitonis, Jason L. Hornick, Leona A. Doyle, Michelle S. Hirsch, Daniel W. Cramer, Ronny Drapkin. Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A11.

Impact of mucinous histology on prognosis for patients with radically resected stage Dukes B2 and C colon cancer: Preliminary results

4126 Background: Previous reports have suggested that mucinous colorectal adenocarcinomas have a poorer prognosis than nonmucinous colorectal adenocarcinomas. This retrospective analysis was conducted to explore whether mucinous carcinoma (MC) is associated with a worse prognosis than nonmucinous carcinoma (NMC) for patients with Dukes B2 and C radically resected colon cancer. Methods: We investigated 1,006 unselected patients who underwent curative surgery for sporadic colon cancer and followed up at six Oncology Department between 1998 and 2006. Univariate and multivariate analyses were performed to determine prognostic factors of survival. Results: MC accounted for 17.9% (n=180) of all colon carcinomas. Patient characteristics were as follows. MC: M/F 104/76; median age, 68 (range, 28–97); pT1/2/3/4, 1/4/153/22; Dukes B2/C 98/82; invasion 26 (14%); ≥12 examined lymph nodes, 115 (64%); adjuvant chemotherapy, 110 (61%). NMC: M/F 445/381; median age, 68 (range, 29–95); pT1/2/3/4, 9/51/715/51; Dukes B2/C 384/442; invasion 199 (24%); ≥12 examined lymph nodes, 499 (60%); adjuvant chemotherapy, 545 (66%). MC were more frequently located in the proximal colon (54.4% versus 34.6% for NMC; p&lt;0.001). No difference between MC and NMC in disease-free survival (hazard ratio, HR 1.01; 95% CI, 0.76–1.36; p=0.92) and overall survival (HR 1.05; 95% CI, 0.74–1.49; p=0.78) was found. After stratification by stage of disease, MC and NMC had no statistically significant difference in 5-year disease-free survival (Dukes B2: 79.1% and 78.1%, respectively, p=0.86; Dukes C: 53.8% and 56.2%, respectively, p=0.58) and overall survival (Dukes B2: 84.2% and 85.5%, respectively, p=0.80; Dukes C: 68.0% and 67.3% p=0.52). Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage at diagnosis (p&lt;0.0001), grading (p&lt;0.0001), and number of lymph node examined (p=0.0002) in the specimen. Conclusions: In this preliminary analysis, patients with mucinous histology who underwent surgery with curative intent for stage Dukes B2 and C colon cancer had similar prognosis compared to NMC. No significant financial relationships to disclose.

Two Subtypes of Mucinous Adenocarcinoma of The Colorectum: Clinicopathological and Genetic Features

This work is aimed at comparing mucinous colorectal adenocarcinomas (MUC) and non-mucinous colorectal adenocarcinomas (non-MUC), and at verifying the existence of two different subgroups of MUC, in terms of clinicopathological features, chromosomal alterations, and outcome, in a geographical area where mucinous colorectal cancer resulted as being very frequent. One hundred and fifty-six unselected patients who underwent curative colorectal resection for sporadic colorectal cancer over a 4-year period were evaluated for histological classification as to MUC and non-MUC subtype, for microsatellite instability (MSI) using six microsatellite markers, and for the presence of p27, Fhit, and cyclooxygenase-2 (Cox-2). Molecular data, immunohistochemical results, recurrence frequency, and patient survival were analyzed statistically in relation to histological subtypes. MUC accounted for 38.5% of all colorectal carcinomas. Compared to non-MUCs, MUCs were more frequently located in the proximal colon (p < 0.001), and more frequently showed MSI phenotype (p < 0.001), altered protein expression of hMlh1 (p = 0.030), Fhit (p <0.001), and p27 (p < 0.001). Compared to MUC with microsatellite-stable (MSS) phenotype, MUC with MSI more frequently resulted as being located in the proximal colon (p = 0.013), and more frequently showed altered expression of hMlh1 (p < 0.001), hMsh2 (p = 0.008), Fhit (p < 0.001), and p27 (p = 0.015). Significantly better survival of patients with proximal MUC (p = 0,012), with MSI MUC (p = 0.017), and with MUC with altered p27 expression (p = 0.02). The results of the present study confirm that MUC represents distinct clinicopathological and genetic features as compared to non-mucinous tumors and support the hypothesis that MUC includes two subtypes with different genetic pathways and behavior.

Mucinous Adenocarcinoma of the Colon and Rectum

Purpose: This study was to evaluate and compare the clinical characteristics of a mucinous adenocarcinoma with those of a non-mucinous adenocarcinoma in colorectal cancer patients. Methods: Data were retrospectively reviewed on 3,232 colorectal cancer patients, including 221 mucinous adenocarcinoma patients (6.1%), who received surgery between 1990 and 2003. Results: The mean tumor size (6.5 cm) of the mucinous adenocarcinomas was bigger than that (5.2 cm) of the non-mucinous adenocarcinomas. The locations of the mucinous adenocarcinomas were 95 (48.2%) in the proximal colon, 35 (17.8%) in the distal colon, and 67 (34.0%) in the rectum whereas those of the non-mucinous adenocarcinomas were 559 (18.9%) in the proximal colon, 861 (29.2%) in the distal colon, and 1,533 (51.9%) in the rectum. Stage distribution was as follows: In mucinous adenocarcinomas, 7 stage A (3.3%), 84 stage B (39.3%), 76 stage C (35.5%), and 47 stage D (21.9%). In non-mucinous adenocarcinomas, 447 stage A (15.2%), 1,036 stage B (35.1%), 997 stage C (33.8%), and 469 stage D (15.9%). In the univariate analysis, the overall 5-year survival rate of patients with a mucinous adenocarcinoma was lower than that of patients with a non-mucinous adenocarcinoma (60% vs. 65%, P=0.016), but survival rates for each stage were not significantly different. The difference in recurrence rates was not statistically significant (33.3% vs. 24.2%, P=0.258). A multivariate analysis showed that the mucinous histologic type was not useful as an independent prognostic factor. Conclusions: Mucinous colorectal adenocarcinomas tend to be large, exist in a proximal location, have an advanced stage at diagnosis. The difference in survival rates for each stage was not statistically significant. A mucinous histologic type was not an independent prognostic factor.

Height and Body Mass Index in Relation to Colorectal and Gallbladder Cancer in Two Million Norwegian Men and Women

The present study aimed at exploring the relations between BMI and stature and colorectal and gallbladder cancer in a huge Norwegian cohort with measured height and weight. Height and weight were measured in two million Norwegian men and women aged 20-74 during 1963-2001. During follow-up, 47,117 colorectal and 1715 gallbladder cancer cases were registered. Relative risks (RRs) of colorectal and gallbladder cancer were estimated using Cox proportional hazards regression. The risk of colon cancer increased with increasing BMI in men; the RR of colon cancer per unit increase in BMI was 1.04 (95% CI: 1.04-1.05). For mucinous colorectal adenocarcinomas, the risk increased to a larger extent with increasing BMI in both sexes. The RR of colorectal cancer associated with 10 cm increase in height was 1.14 (95% CI: 1.11-1.16) in men and 1.17 (95% CI: 1.14-1.20) in women. The risk of gallbladder cancer increased with increasing BMI in women; the overall RR associated with one unit increase in BMI was 1.06 (95% CI: 1.04-1.07). There was no association between height and gallbladder cancer in either sex. The risk of colon cancer increased with increasing BMI in men, and the risk of gallbladder cancer increased with increasing BMI in women. In both sexes, the risk of colon cancer increased with increasing height.

Usefulness of Cdx2 in Separating Mucinous Bronchioloalveolar Adenocarcinoma of the Lung From Metastatic Mucinous Colorectal Adenocarcinoma

We studied the diagnostic value of Cdx2 to distinguish mucinous bronchioloalveolar carcinoma from mucinous colorectal adenocarcinoma metastatic to the lung. We retrieved 92 via the hospital computer system, including 30 mucinous bronchioloalveolar carcinomas, 32 nonmucinous bronchioloalveolar carcinomas, and 30 mucinous colorectal adenocarcinomas metastatic to the lung. All cases were confirmed by clinical history and surgical resection with occasional immunohistochemical studies. Cases were stained with antibodies against Cdx2, thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7, and CK20. Bronchioloalveolar carcinoma, mucinous type, showed positive staining for Cdx2, TTF-1, CK7, and CK20 in 0 (0%), 5 (17%), 30 (100%), and 18 (60%) of 30 cases, respectively; nonmucinous tumors were positive in 0 (0%), 30 (94%), 32 (100%), and 0 (0%) of 32 cases, respectively. For colorectal adenocarcinoma, the positive staining for Cdx-2, TTF-1, CK7, and CK20 was 29 (97%), 0 (0%), 7 (23%), and 29 (97%) of 30 cases, respectively. Our results demonstrated Cdx2 as a sensitive and specific marker for differentiating metastatic colorectal adenocarcinoma from mucinous bronchioloalveolar adenocarcinoma.

Usefulness of Cdx2 in separating mucinous bronchioloalveolar adenocarcinoma of the lung from metastatic mucinous colorectal adenocarcinoma.

We studied the diagnostic value of Cdx2 to distinguish mucinous bronchioloalveolar carcinoma from mucinous colorectal adenocarcinoma metastatic to the lung. We retrieved 92 via the hospital computer system, including 30 mucinous bronchioloalveolar carcinomas, 32 nonmucinous bronchioloalveolar carcinomas, and 30 mucinous colorectal adenocarcinomas metastatic to the lung. All cases were confirmed by clinical history and surgical resection with occasional immunohistochemical studies. Cases were stained with antibodies against Cdx2, thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7, and CK20. Bronchioloalveolar carcinoma, mucinous type, showed positive staining for Cdx2, TTF-1, CK7, and CK20 in 0 (0%), 5 (17%), 30 (100%), and 18 (60%) of 30 cases, respectively; nonmucinous tumors were positive in 0 (0%), 30 (94%), 32 (100%), and 0 (0%) of 32 cases, respectively. For colorectal adenocarcinoma, the positive staining for Cdx-2, TTF-1, CK7, and CK20 was 29 (97%), 0 (0%), 7 (23%), and 29 (97%) of 30 cases, respectively. Our results demonstrated Cdx2 as a sensitive and specific marker for differentiating metastatic colorectal adenocarcinoma from mucinous bronchioloalveolar adenocarcinoma.