Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.

Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry. Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression. TP53 , APC , and KRAS were the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewer KRAS (OR=0.64, 95%CI=0.41-0.97, p=0.037) and PIK3CA mutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation in KNCN (OR=1.34, 95%CI=1.09-1.66, p=5.74×10 -3 ) and TMEM184B (OR=1.53, 95%CI=1.10-2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status in CDC27 (LRT p=0.0084) and between SMAD2 mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048). Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities. Significance: Our data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.

A clinical overview of people living with HIV and genitourinary cancer care.

The number of people living with HIV infection has been increasing globally. Administration of antiretroviral therapy is effective in controlling the infection for most patients and, as a consequence, people living with HIV (PLWH) now often have a long life expectancy. However, their risk of developing cancer - most notably virus-related cancers - has been increasing. To date, few studies have assessed the risk of genitourinary cancers in PLWH, and robust scientific data on their treatment-related outcomes are lacking. Previous studies have noted that PLWH are at a reduced risk of prostate cancer; however, low adoption and/or availability of prostate cancer screening among these patients might be confounding the validity of this finding. In genitourinary cancers, advanced stage at diagnosis and reduced cancer-specific mortality have been reported in PLWH. These data likely reflect, at least in part, the inequity of health care access for PLWH. Notably, systemic chemotherapy and/or radiotherapy could decrease total CD4+ cell counts, which could, therefore, increase the risk of morbidity and mortality from cancer treatments in PLWH. Immune checkpoint inhibitors have become the therapeutic backbone for many advanced malignancies in the general population; however, most studies validating their efficacy have excluded PLWH owing to concerns of severe adverse effects from immune checkpoint inhibitors themselves and/or related to their immunosuppressed status. To our knowledge, no genitourinary cancer survivorship programme exists that specifically caters to the needs of PLWH. By including PLWH in ongoing cancer trials, we can gain invaluable insights that will help to improve cancer care specifically for PLWH.

Return to intended oncologic therapy after colectomy for stage III colon adenocarcinoma: Does surgical approach matter?

AIM: Return to intended oncologic treatment (RIOT) is an important paradigm for surgically resected cancers requiring multimodal treatment. Benefits of minimally invasive colectomy (MIC) may allow earlier initiation of adjuvant chemotherapy (ACT) and have associated survival benefits. We sought to determine if operative approach affects RIOT timing in resected stage III colon cancer. METHODS: NCDB identified pathological stage III colon adenocarcinoma patients who underwent resection and received ACT. Propensity score matching and kernel density estimation compared operative approaches and conversion impact on intervals to RIOT. RESULTS: A total of 15,132 open colectomies (OC) versus 14,107 MIC were included. MIC patients had two-days shorter median length of stay (LOS) (4 vs. 6 days; p < 0.001), one-week shorter median time to RIOT (6 vs. 7 weeks; p = 0.015) comparing 12,867 matched pairs. There was no difference in time interval to RIOT between the LC versus RC, converted MIC vs. OC groups. MIC was a favourable predictor of earlier RIOT (HR 1.14 [1.07-1.22]; p < 0.001). CONCLUSION: MIC in stage III colon cancer is associated with a shorter time to RIOT when compared to OC. Since timely initiation of ACT may influence cancer outcome, MIC may be oncologically preferable. Prospective studies are needed to assess RIOT and survival outcomes in stage III colon cancer.

Oncologists' experiences caring for LGBTQ patients with cancer: Qualitative analysis of items on a national survey.

OBJECTIVES: Sexual and gender minority (SGM) individuals experience cancer-related health disparities and reduced quality of cancer care compared to the general population in part due to a lack of knowledgeable providers. This study explored oncologists' experiences and perspectives in providing patient-centered care for SGM individuals with cancer. METHODS: We conducted a qualitative analysis of oncologists' responses to four open-ended items on a national survey eliciting their experiences, reservations, and suggestions in treating SGM patients. RESULTS: Over 50 % of the 149 respondents of the national survey responded to at least one open-ended item. Many oncologists reported positive experiences reflecting personal growth and affirmative care practices, such as open, non-judgmental communication, compassion, competence, and supporting patients' identity. There was a notable lack of experience with transgender patients in particular. Lack of knowledge, interpersonal communication concerns (e.g., fear of offending patients), and microaggressions ("don't ask, don't tell") were identified as barriers to providing affirming care. CONCLUSIONS: Oncologists recognize their knowledge deficits and need strategies to overcome communication barriers and microaggressions among the cancer care team to provide SGM-affirming care. PRACTICE IMPLICATIONS: Curricula are needed to train oncologists in SGM healthcare needs and affirming communication skills to facilitate patient-centered care for SGM individuals with cancer.

Evaluation of Factors Associated With Successful Matriculation to Colon and Rectal Surgery Fellowship.

BACKGROUND: As an increasing number of general surgery residents apply for fellowship positions, it is important to identify factors associated with successful matriculation. For applicants to colon and rectal surgery, there are currently no objective data available to distinguish which applicant attributes lead to successful matriculation. OBJECTIVE: The purpose of this study was to identify objective factors that differentiate colon and rectal surgery fellowship applicants who successfully matriculate with those who apply but do not matriculate. DESIGN: This was a retrospective analysis of colon and rectal surgery applicant characteristics. SETTINGS: Deidentified applicant data provided by the Association of American Medical Colleges from 2015 to 2017 were included. MAIN OUTCOME MEASURES: Applicant demographics, medical school and residency factors, number of program applications, number of publications, and journal impact factors were analyzed to determine associations with successful matriculation. RESULTS: Most applicants (n = 371) and subsequent matriculants (n = 248) were white (61%, 62%), male (65%, 63%), US citizens (80%, 88%) who graduated from US allopathic medical schools (66%, 75%). Statistically significant associations included graduation from US allopathic medical schools (p < 0.0001), US citizenship (p < 0.0001), and number of program applications (p = 0.0004). Other factors analyzed included American Osteopathic Association membership (p = 0.57), university-based residency (p = 0.51), and residency association with a colon and rectal surgery training program (p = 0.89). Number of publications and journal impact factors were not statistically different between cohorts (p = 0.067, p = 0.150). LIMITATIONS: American Board of Surgery In-Training Examination scores, rank list, and subjective characteristics, such as strength of interview and letters of recommendation, were not available using our data source. CONCLUSIONS: Successful matriculation to a colon and rectal surgery fellowship program was found to be associated with US citizenship, graduation from a US allopathic medical school, and greater number of program applications. The remaining objective metrics analyzed were not associated with successful matriculation. Subjective and objective factors that were unable to be measured by this study are likely to play a determining role. See Video Abstract at http://links.lww.com/DCR/B415. EVALUACIN DE FACTORES VINCULADOS EN LA INMATRICULACIN EXITOSA PARA BECAS DE CIRUGA COLORRECTAL: ANTECEDENTES:A medida que un número cada vez mayor de residentes de Cirugía General solicitan una beca, es importante identificar los factores vinculados con una inmatriculación exitosa. Para los candidatos a una beca en Cirugía Colorrectal, hoy en día no existen datos objetivos disponibles para distinguir qué atributos del solicitante conducen a una inmatriculación exitosa.OBJETIVO:Identificar objetivamente los factores que diferencian un candidato a una beca en Cirugía Colorrectal que se inmatricula con éxito de aquel que aplica pero no llega a inmatricularse.DISEÑO:Análisis retrospectivo de las características de los solicitantes de beca para Cirugía Colorrecatl.AJUSTES:Datos de los solicitantes no identificados, proporcionados por la Asociación de Colegios Médicos Estadounidenses de 2015 a 2017.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron los factores demográficos del solicitante, las facultades de medicina y los factores de la residencia, el número de solicitudes de programas, el número y el factor de impacto de las publicaciones realizadas para determinar la asociación con una inmatriculación exitosa.RESULTADOS:La mayoría de los solicitantes (n = 371) que posteriormente fueron inmatriculados exitosamente (n = 248) eran blancos (61%, 62%, respectivamente), hombres (65%, 63%), ciudadanos estadounidenses (80%, 88%) que se graduaron de Facultades de medicina alopática en los EE. UU. (66%, 75%). Las asociaciones estadísticamente significativas incluyeron la graduación de las escuelas de medicina alopática de los EE. UU. (P <0,0001), la ciudadanía de los EE. UU. (P <0,0001) y el número de solicitudes de programas (p = 0,0004). Otros factores analizados incluyeron: membresía AOA (p = 0,57), la residencia universitaria (p = 0,51) y asociación de la residencia con un programa de formación en Cirugía Colorrectal (p = 0,89). El número de publicaciones y los factores de impacto de las revistas no fueron estadísticamente diferentes entre las cohortes (p = 0,067, p = 0,15, respectivamente).LIMITACIONES:El Score ABSITE, la posición en lista de clasificación y las características subjetivas como el de una buena entrevista y las cartas de recomendación no se encontraban disponibles en la fuente de datos.CONCLUSIONES:Se encontró que la inmatriculación exitosa a un programa de becas de Cirugía Colorreectal estaba asociada con la ciudadanía estadounidense, la graduación en una Facultad de medicina alopática en los EE. UU, y al mayor número de solicitudes de programas. El analisis de las medidas objetivas restantes no se asociaron con una inmatriculación exitosa. Es probable que los factores subjetivos y objetivos que no pudieron ser medidos por este estudio jueguen un papel determinante. Consulte Video Resumen en http://links.lww.com/DCR/B415. (Traducción-Dr Xavier Delgadillo).

Two-step unconventional protocol for epitaxial growth in one dimension with hindered reactions.

We study the effect of hindered aggregation and/or nucleation on the island formation process in a two-step growth protocol. In the proposed model, the attachment of monomers to islands and/or other monomers is hindered by additional energy barriers which decrease the hopping rate of the monomers to the occupied sites of the lattice. For zero and weak barriers, the attachment is limited by diffusion while for strong barriers it is limited by reaction. We describe the time evolution of the system in terms of the monomer and island densities, N_{1} and N. We also calculate the gap length, the capture zone and the island distributions. For all the sets of barriers considered, the results given by the proposed analytical model are compared with those from kinetic Monte Carlo simulations. We found that the behavior of the system depends on the ratio of the nucleation barrier to the aggregation barrier. The two-step growth protocol allows more control and understanding on the island formation mechanism because it intrinsically separates the nucleation and aggregation processes in different time regimes.

National Survey of Oncologists at National Cancer Institute-Designated Comprehensive Cancer Centers: Attitudes, Knowledge, and Practice Behaviors About LGBTQ Patients With Cancer.

PURPOSE: To identify potential gaps in attitudes, knowledge, and institutional practices toward lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) patients, a national survey of oncologists at National Cancer Institute-Designated Comprehensive Cancer Centers was conducted to measure these attributes related to LGBTQ patients and desire for future training and education. METHODS: A random sample of 450 oncologists from 45 cancer centers was selected from the American Medical Association's Physician Masterfile to complete a survey measuring attitudes and knowledge about LGBTQ health and institutional practices. Results were quantified using descriptive and stratified analyses and by a novel attitude summary measure. RESULTS: Of the 149 respondents, there was high agreement (65.8%) regarding the importance of knowing the gender identity of patients, which was contrasted by low agreement (39.6%) regarding the importance of knowing sexual orientation. There was high interest in receiving education regarding the unique health needs of LGBTQ patients (70.4%), and knowledge questions yielded high percentages of "neutral" and "do not know or prefer not to answer" responses. After completing the survey, there was a significant decrease ( P < .001) in confidence in knowledge of health needs for LGB (53.1% agreed they were confident during survey assessment v 38.9% postsurvey) and transgender patients (36.9% v 19.5% postsurvey). Stratified analyses revealed some but limited influence on attitudes and knowledge by having LGBTQ friends and/or family members, political affiliation, oncology specialty, years since graduation, and respondents' region of the country. CONCLUSION: This was the first nationwide study, to our knowledge, of oncologists assessing attitudes, knowledge, and institutional practices of LGBTQ patients with cancer. Overall, there was limited knowledge about LGBTQ health and cancer needs but a high interest in receiving education regarding this community.

Island size distribution with hindered aggregation.

We study the effect of hindered aggregation on the island formation processes for a one-dimensional model of epitaxial growth with arbitrary nucleus size i. In the proposed model, the attachment of monomers to islands is hindered by an aggregation barrier, ε_{a}, which decreases the hopping rate of monomers to the islands. As ε_{a} increases, the system exhibits a crossover between two different regimes; namely, from diffusion-limited aggregation to attachment-limited aggregation. The island size distribution, P(s), is calculated for different values of ε_{a} by a self-consistent approach involving the nucleation and aggregation capture kernels. The results given by the analytical model are compared with those from kinetic Monte Carlo simulations, finding a close agreement between both sets of data for all considered values of i and ε_{a}. As the aggregation barrier increases, the spatial effect of fluctuations on the density of monomers can be neglected and P(s) smoothly approximates to the limit distribution P(s)=δ_{s,i+1}. In the crossover regime the system features a complex and rich behavior, which can be explained in terms of the characteristic timescales of different microscopic processes.

Culturally Competent Care for Sexual and Gender Minority Patients at National Cancer Institute-Designated Comprehensive Cancer Centers.

PURPOSE: This study sought to identify the policies and guidelines regarding culturally competent care of sexual and gender minority (SGM) cancer patients and survivors at National Cancer Institute (NCI)-Designated Comprehensive Cancer Centers. METHODS: This study used an in-depth interview qualitative approach. Semistructured interviews were conducted via telephone with representatives from 21 of the 45 NCI-Designated Comprehensive Cancer Centers in 2015. Verbatim transcripts were created from the audiotapes for content analysis. RESULTS: Two main themes were identified as follows: (1) patient-focused experiences and support and (2) organization-focused development activities. Most of the cancer centers in this study had an advisory committee to assist with SGM policies and guidelines. Despite the existence of these committees, the majority of centers did not have explicit policies, guidelines, or routine practices addressing the following issues: the collection and integration of sexual orientation and gender identity information in the medical record, gender-neutral language on patient forms, patient educational materials with SGM-specific health concerns, SGM-specific support for cancer survivors, or required SGM-specific cultural competency trainings for medical and nonmedical staff. CONCLUSION: In general, the cancer centers in this study lacked institutional policies, guidelines, and practices focused on patient-centered cancer care for SGM populations. Coordinated efforts are needed to systemically improve patient-centered cancer care for these populations.

Cancer and the LGBTQ Population: Quantitative and Qualitative Results from an Oncology Providers' Survey on Knowledge, Attitudes, and Practice Behaviors.

BACKGROUND: Despite growing social acceptance, the LGBTQ population continues to face barriers to healthcare including fear of stigmatization by healthcare providers, and providers' lack of knowledge about LGBTQ-specific health issues. This analysis focuses on the assessment of quantitative and qualitative responses from a subset of providers who identified as specialists that treat one or more of the seven cancers that may be disproportionate in LGBTQ patients. METHODS: A 32-item web-based survey was emailed to 388 oncology providers at a single institution. The survey assessed: demographics, knowledge, attitudes, and practice behaviors. RESULTS: Oncology providers specializing in seven cancer types had poor knowledge of LGBTQ-specific health needs, with fewer than half of the surveyed providers (49.5%) correctly answering knowledge questions. Most providers had overall positive attitudes toward LGBTQ patients, with 91.7% agreeing they would be comfortable treating this population, and would support education and/or training on LGBTQ-related cancer health issues. CONCLUSION: Results suggest that despite generally positive attitudes toward the LGBTQ population, oncology providers who treat cancer types most prevalent among the population, lack knowledge of their unique health issues. Knowledge and practice behaviors may improve with enhanced education and training on this population's specific needs.

Oncology healthcare providers' knowledge, attitudes, and practice behaviors regarding LGBT health.

OBJECTIVE: There are limited data on lesbian, gay, bisexual, and transgender (LGBT) healthcare experiences and interactions with the providers. This study assessed knowledge, attitudes, and practice behaviors of oncology providers regarding LGBT health. METHODS: A 32-item web-based survey was emailed to 388 oncology providers at a single institution. The survey assessed: demographics, knowledge, attitudes, and practice behaviors. RESULTS: 108 providers participated in the survey (28% response rate). <50% answered knowledge questions correctly. 94% stated they were comfortable treating this population. 26% actively inquired about a patient's sexual orientation when taking a history. 36% felt the need for mandatory education on LGBT cultural competency at the institution. Results from the open comments section identified multiple misconceptions. CONCLUSION: This study revealed knowledge gaps about LGBT health risks. Cultural competency training may aid oncology providers to understand the need to inquire about patients' gender identity and sexual orientation. PRACTICE IMPLICATIONS: Health care providers who incorporate the routine collection of gender identity and sexual orientation (SOGI) in their patient history taking may improve patient care by offering tailored education and referrals. While identifying as LGBT does not in itself increase risk for adverse health outcomes, this population tends to have increased risk behaviors.

Cancer and lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations.

This article provides an overview of the current literature on seven cancer sites that may disproportionately affect lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations. For each cancer site, the authors present and discuss the descriptive statistics, primary prevention, secondary prevention and preclinical disease, tertiary prevention and late-stage disease, and clinical implications. Finally, an overview of psychosocial factors related to cancer survivorship is offered as well as strategies for improving access to care.

BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis.

BACKGROUND: Colorectal cancer is a heterogeneous disease with multiple underlying genetic mutations causing different clinical phenotypes. Mutation in the BRAF oncogene is a key step in malignant transformation within the methylator pathway to colorectal cancer. However, there is a paucity of information about BRAF mutant colorectal tumors. OBJECTIVE: This study defines the clinical characteristics and oncologic outcome associated with colorectal cancer BRAF mutations. DESIGN: Colorectal adenocarcinomas from a single-institution frozen-tumor biobank were studied. Genomic DNA was isolated and analyzed for mutations in the BRAF oncogene by polymerase chain reaction amplification followed by direct sequencing. A sample was classified as mutant if any of the tested loci were mutated. Patient and tumor characteristics were recorded including patient age, sex, tumor location, tumor differentiation, and microsatellite instability. MAIN OUTCOME MEASURES: Statistical associations with BRAF mutant tumors were determined by the Fisher exact probability test, χ test, or Wilcoxon analysis. Kaplan-Meier estimates and multivariate Cox regression analysis were performed for overall survival. RESULTS: Four hundred seventy-five colorectal adenocarcinomas were included in the study population; 56 samples harbored a BRAF mutation (12%). There were significant differences between BRAF wild-type and mutant tumors in age (66 vs 75 years, p = 0.004), female sex (44% vs 71%, p < 0.001), proximal tumor location (44% vs 95%, p < 0.001), and frequency of microsatellite instability (16% vs 76%, p < 0.001). There was no difference in cancer stage between BRAF mutant and wild-type populations. Survival data were analyzed for 322 patients with stage I to III disease, and patients with a BRAF mutation had decreased overall survival than those without a mutation (p = 0.018). With the use of Cox regression analysis, BRAF mutation conferred a worse overall survival (HR 1.79, CI 1.05-3.05, p = 0.03) independent of microsatellite instability status. CONCLUSIONS: BRAF mutations in colorectal cancers are associated with distinct clinical characteristics and worse prognosis.

Relative role of methylator and tumor suppressor pathways in ulcerative colitis-associated colon cancer.

BACKGROUND: Chronic ulcerative colitis (UC) is associated with an increased colorectal cancer risk which may be secondary to repetitive mucosal injury. Both epigenetic methylation and the classic adenoma-to-carcinoma sequence have been implicated in this malignant transformation, but the underlying molecular mechanisms remain poorly defined. This study compares the molecular characteristics of colitis-associated and common colorectal cancers. METHODS: Nineteen patients with colorectal adenocarcinomas arising within UC were matched for age and cancer site with 54 patients with sporadic adenocarcinomas. Tumor tissue was examined for BRAF mutations, CpG island methylator phenotype (CIMP), and MLH1 promoter methylation. Mutations of KRAS and p53 were assessed by sequencing. RESULTS: Patient demographics were similar for the two groups. CIMP was observed in 22% of sporadic colorectal cancers and in 5% of UC cancers (P = 0.162). Rates of BRAF mutation (4% vs 5%, P = 1.0), MLH1 methylation (9% versus 5%, P = 0.682), and KRAS mutations (24% versus 32%, P = 0.552) were similar between the groups. However, colitis-associated colorectal cancers were more likely to have a p53 mutation compared to sporadic adenocarcinomas (95% versus 53%, P = 0.001). The dominant mutation for colitis-associated cancers was a mutation in codon 4, representing half of the mutations. Furthermore, colitis-associated cancers had a higher rate of mutation in codon 8 (48% versus 6%, P < 0.001) than sporadic counterparts. CONCLUSIONS: Unlike other inflammatory gastrointestinal cancers, colitis-associated colorectal cancers do not preferentially arise via a methylator pathway when compared to sporadic colorectal cancers. Chromosomal instability remains an important etiology, but with a unique p53 frequency and mutation pattern.

Divergent oncogenic changes influence survival differences between colon and rectal adenocarcinomas.

PURPOSE: Colorectal cancers develop through various mechanisms such as chromosomal instability, DNA mismatch repair deficiency (microsatellite instability), and epigenetic DNA promoter methylation (CpG island methylator phenotype). This study evaluated the disparity in neoplastic changes between colon and rectal cancers. METHODS: A clinic-based colorectal frozen tumor bank at a single institution was queried for colon and rectal adenocarcinomas. Tumor DNA was extracted and analyzed for microsatellite instability, methylation, and mutations in the oncogenes KRAS and BRAF. Patient demographics, tumor characteristics, and clinical outcomes were compared. RESULTS: The 268 patients with colon cancer and 89 with rectal cancer were similar in gender, tumor size, stage, and differentiation. Colon cancers had a higher incidence of microsatellite instability (27 percent) and methylator phenotype (28 percent) compared with rectal cancers (7 percent, 3 percent, respectively; P < 0.001). Although KRAS mutation rate was similar, colon cancers had a higher incidence of BRAF mutations (16.7 percent vs. 0 percent; P < 0.001). Microsatellite stable tumors had an increased risk of disease recurrence compared with microsatellite unstable tumors (odds ratio, 3.86). Despite overall differences in outcome between colon and rectal cancers, no significant difference in survival existed when similar molecular phenotypes were compared across anatomic sites. CONCLUSIONS: Although colon cancers are molecularly heterogeneous, rectal cancers arise mostly via a single neoplastic pathway. Genetic and molecular differences influence prognosis more than anatomic location and suggest that oncogenic pathways contribute to survival differences between colon and rectal cancers.

Identifying Lynch syndrome: we are all responsible.

PURPOSE: The Amsterdam criteria and Bethesda guidelines are used to identify patients with Lynch syndrome. A family history of Lynch syndrome-related cancers or histopathology suggestive of microsatellite instability should prompt responses by the pathologist and clinician. This study evaluated the impact of microsatellite instability pathology findings on Lynch syndrome evaluation by clinicians. METHODS: Microsatellite unstable tumors were identified from a maintained tissue bank, and MLH1 methylation was determined. Clinical information and management recommendations by the pathologist and clinician were collected from the medical record. RESULTS: Fifty-one patients with microsatellite unstable colorectal tumors were identified between 2003 and 2006. Thirteen (25 percent) patients were appropriately referred for additional testing, including eight with documented microsatellite instability histology and five based on history alone. Thirty-seven (73 percent) patients with microsatellite unstable tumors were not detected by pathologists or clinicians, and no additional workup for Lynch syndrome was performed. Two patients met Amsterdam criteria and represent potentially missed Lynch syndrome. CONCLUSIONS: Microsatellite instability-H histology was the driving force for the Lynch syndrome evaluation. Histopathology alone failed to identify all potential Lynch syndrome patients. Omission of an adequate familial risk assessment may lead to missed diagnosis of Lynch syndrome when suspicious histopathology fails to trigger appropriate testing.