Impact of Endoscopic Treatment in Severe Duodenal Polyposis: A National Study in Familial Adenomatous Polyposis Patients.

BACKGROUND & AIMS: The majority of patients with familial adenomatous polyposis (FAP) develop duodenal adenomas with a risk of progression to duodenal cancer. Endoscopic management of FAP duodenal adenomas has been proposed as a less-invasive option than surgery, but available data still are limited. Our aims were to assess the feasibility and safety of endoscopic treatment in duodenal polyposis and to evaluate its long-term efficacy in terms of recurrence and malignant degeneration. METHODS: FAP patients with stage IV duodenal polyposis were enrolled in 5 French centers as part of a national cohort and followed up for a median period of 5.66 years (interquartile range, 6.39 y). Primary outcomes were duodenal surgery-free and cancer-free survival. Two groups of patients were identified according to endoscopic procedures: group 1: resection and or destruction (by argon plasma coagulation) of duodenal polyps, and group 2: papillectomy. RESULTS: Fifty-eight patients were enrolled (29 men; median age, 44 y). Endoscopic therapy was performed in 37 patients in group 1 and in 19 patients in group 2. Duodenal cancer-free and surgery-free survival were 95.8% at 5 years and 92.6% at 10 years. Four patients required surgery and 2 patients developed cancers. In the 58 patients, the calculated Spigelman score decreased from 9.24 points at entry to 6.35 at 5 years and then plateaued. Complications (mostly bleeding and perforation) occurred in 20 patients. CONCLUSIONS: In this long-term cohort follow-up evaluation, endoscopic treatment of patients with severe duodenal polyposis appears relatively safe and effective as an alternative to surgery for the prevention of cancer.

A de novo pathogenic variant in the MSH6 gene in a 52 years-old woman.

Lynch syndrome (LS) is a condition which predisposes individuals primarily to early-onset colorectal and endometrial cancer. LS is characterized by a germline pathogenic variant in one of the MMR (MisMatch Repair) gene, inducing a phenotype of microsatellite instability in the tumor, which may be associated with a loss of expression of MMR proteins detected by standard immunohistochemistry on tumor tissue. Most of the time, LS is inherited from a parent in whom the condition may not be known due to incomplete penetrance, but de novo pathogenic variant is a rare occurrence. Here, we describe the case of a 52-year-old woman with no family history of LS, referred to the genetics department for colorectal cancer at the age of 50. Genetic analysis revealed a de novo germline pathogenic variant in the MSH6 gene. To date, this case is only the second report of a de novo pathogenic variant in the MSH6 gene in Lynch syndrome. De novo mutations have been extensively studied over the past years, but little is known about their origin and mechanism of occurrence in MMR genes. However, knowledge of mutation status allows better cancer risk management for the patient and an appropriate genetic testing and counseling for her family.

Exploring the factors influencing adherence to oral anticancer drugs in patients with digestive cancer: a qualitative study.

PURPOSE: The aim of this study was to explore the beliefs, perceptions and representations of patients in order to identify the determinants of oral anticancer drugs adherence and to take action in current practice to improve patient support in digestive oncology. METHODS: We constructed a semi-directed interview guide which aimed to explore the patient's relationship with medication, their health history, their experiences at the time of the announcement of treatment, their confidence, their fears, their motivations to adhere to their treatment and the constraints linked to their treatment. The data were analysed and discussed using a thematic approach. RESULTS: Seventeen patients agreed to participate in the study. The median age was 60 years. Ten patients had colorectal cancer, 3 patients had hepatocellular carcinoma, 3 patients had gastrointestinal stromal tumour and 1 patient had neuroendocrine pancreatic tumour. We identified five categories of factors influencing adherence: demographic and socioeconomic, disease-related, treatment-related, care system-related, and patient representation and pathways' factors. A majority of patients emphasised the importance of family support in the adherence process and the convenience of per os treatment compared to other intravenous treatments. However, several negative determinants emerged such as the toxicity of the treatment, fears of forgetting to take the medication, difficulties with the galenic formulation and negative beliefs of the family. CONCLUSION: This study demonstrates the need to address the different dimensions of the patient in order to understand his or her behaviour with regard to adherence and to identify the levers for improvement.

Targeting DNA Damage Repair Mechanisms in Pancreas Cancer.

Impaired DNA damage repair (DDR) is increasingly recognised as a hallmark in pancreatic ductal adenocarcinoma (PDAC). It is estimated that around 14% of human PDACs harbour mutations in genes involved in DDR, including, amongst others, BRCA1/2, PALB2, ATM, MSH2, MSH6 and MLH1. Recently, DDR intervention by PARP inhibitor therapy has demonstrated effectiveness in germline BRCA1/2-mutated PDAC. Extending this outcome to the significant proportion of human PDACs with somatic or germline mutations in DDR genes beyond BRCA1/2 might be beneficial, but there is a lack of data, and consequently, no clear recommendations are provided in the field. Therefore, an expert panel was invited by the European Society of Digestive Oncology (ESDO) to assess the current knowledge and significance of DDR as a target in PDAC treatment. The aim of this virtual, international expert meeting was to elaborate a set of consensus recommendations on testing, diagnosis and treatment of PDAC patients with alterations in DDR pathways. Ahead of the meeting, experts completed a 27-question survey evaluating the key issues. The final recommendations herein should aid in facilitating clinical practice decisions on the management of DDR-deficient PDAC.

Evaluation of a Phone Call Reminder Strategy in the Surveillance of Patients with Gastric Precancerous Lesions Lost to Follow-Up.

BACKGROUND: Surveillance of gastric precancerous lesions (GPL) may reduce gastric cancer (GC)-related mortality, but some patients with GPL are lost to follow-up. OBJECTIVE: The aim of this study was to evaluate the feasibility and efficacy of a "phone-call" strategy in surveillance of the lost to follow-up patients. PATIENTS AND METHODS: Among all the patients diagnosed with GPL (atrophic gastritis, intestinal metaplasia, low-grade dysplasia) between 2000 and 2015, we identified those who should undergo surveillance endoscopy according to the current guidelines. They were contacted by telephone and invited to undergo endoscopy with gastric biopsies for histological analysis. RESULTS: Among 535 patients with GPL, 134 were contacted. Sixty-two (46%) could not be joined, 36 did not have endoscopy for other reasons, and finally, 36 patients (22 males, median age 65 years) were included. After the median time interval of 57 months between 2 endoscopies, 18 patients showed stability, 11 regression, and 7 progression of GPL, including 1 patient who developed GC. CONCLUSION: Despite several telephone calls, only one-third of the contacted patients could be brought to surveillance endoscopy. Most of the patients showed stability of GPL, but 1 progressed to GC and could be successfully treated.

Long-Term Follow-up of Gastric Precancerous Lesions in a Low GC Incidence Area.

INTRODUCTION: Data on the evolution of gastric precancerous lesions (GPL), especially in countries of a Low gastric cancer incidence area are limited. Our objective was to study a long-term evolution of GPL in France. METHODS: All the patients diagnosed with GPL (atrophic gastritis, intestinal metaplasia [IM], and dysplasia) between 2000 and 2015 and fulfilling criteria for evolution assessment (at least 2 endoscopies, minimal follow-up of 6 months, and at least 2 biopsies obtained from the antrum and corpus) were included. Clinical and endoscopic data were analyzed, and histological samples were reviewed by an expert pathologist with evaluation of the Operative Link on Gastric Intestinal Metaplasia Assessment stage and type of IM. RESULTS: From the 507 patients with GPL, 79 fulfilled the strict criteria. During a mean follow-up of 66 months, during which the patients had a mean number of 4 endoscopies (min-max: 2-21) with 9 biopsies/endoscopy, a stability was observed in 70% of patients. Progression occurred in 14% of patients, within a mean delay of 62.1 months (min-max: 17-99). Progression of the lesions was significantly higher in patients with incomplete type of IM (relative risk of progression for incomplete IM: 11.5; 95% confidence interval 2.5-53.1). Regression of IM occurred in 16% of the patients, after a mean delay of 90 months. DISCUSSION: This study shows that the patients with antrum-limited IM, especially of incomplete type, are at the highest risk of developing gastric cancer. In most patients, however, the lesions remain stable, which highlights the need for additional markers to better target the patients at risk of progression.

Bringing Greater Accuracy to Europe's Healthcare Systems: The Unexploited Potential of Biomarker Testing in Oncology.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. This paper sets out the potential of biomarker testing, the unfolding precision and range of possible diagnosis and prediction, and the many obstacles to adoption. It offers case studies of biomarker testing in breast, ovarian, prostate, lung, thyroid and colon cancers, and derives specific lessons as to the potential and actual use of each of them. It also draws lessons about how to improve access and alignment, and to remedy the data deficiencies that impede development. And it suggests solutions to outstanding issues - notably including funding and the tangled web of obtaining reimbursement or equivalent coverage that Europe's fragmented health system implies. It urges a European evolution towards an initial minimum testing scenario, which would guarantee universal access to a suite of biomarker tests for the currently most common conditions, and, further into the future, to an optimum testing scenario in which a much wider range of biomarker tests would be introduced and become part of a more sophisticated health system articulated around personalised medicine. For exploiting genomics to the full, it argues the need for a new policy framework for Europe. Biomarker testing is not an issue that can be treated in isolation, since the purpose of testing is to improve health. Its use is therefore always closely linked to specific health challenges and needs to be viewed in the broader policy context in the EU and more widely. The paper is the result of extensive engagement with experts and decision makers to develop the framework, and consequently represents a wide consensus of views on how healthcare systems should respond from push and pull factors at local, national and cross-border and EU level. It contains strong views and clear recommendations springing from the convictions of patients, clinicians, academics, medicines authorities, HTA bodies, payers, the diagnostic, pharmaceutical and ICT industries, and national policy makers.

Prevalence, Characteristics and Endoscopic Management of Gastric Premalignant Lesions in France.

INTRODUCTION: Surveillance of gastric precancerous lesions (GPL) is recommended, but the data on their clinical and endoscopic management in a "real-life" practice are limited. Our aim was to study the modalities of endoscopic management of patients with GPL in France. DESIGN: All the patients diagnosed with GPL in our center between 2000 and 2015 were grouped and analyzed according to the most severe GPL found, in the following order: atrophic gastritis only (AG), intestinal metaplasia (IM), low grade dysplasia (LGD), high grade dysplasia (HGD). RESULTS: Out of 16,764 patients having undergone upper endoscopy with gastric biopsies, 507 were identified with GPL (detection rate 3.2%). Overall, Helicobacter pylori infection was found in 41% of patients. IM was by far the most frequently found lesion (79%), followed by LGD (17%), HGD (2%), and AG only (2%). H. pylori infection rate was decreasing, while the age of the patients was increasing, together with the increasing severity of GPL (p = 0.005). Only 28% of the patients had at least one follow-up endoscopy. No correlation was found between the endoscopist's appreciation of the mucosa and histological results. CONCLUSION: In France, GPL can be expected in about 3% of patients undergoing upper endoscopy with gastric biopsies for any reason. The correlation between the endoscopic evaluation and histology is poor. Spreading of published guidelines should improve the management of patients with GPL in the future.

Endoscopic Phenotype of Monoallelic Carriers of MUTYH Gene Mutations in the Family of Polyposis Patients: A Prospective Study.

BACKGROUND: Almost no prospective data on endoscopy in MUTYH monoallelic carriers are available. OBJECTIVE: This study aimed to define the prevalence of colorectal and duodenal adenomas in a population of people presenting with a single mutation of the MUTYH gene and being first-degree relatives of biallelic MUTYH mutation carriers. DESIGN: This study is a prospective cohort evaluation. PATIENTS: Patients were first-degree relatives of a patient who had polyposis with biallelic MUTYH mutation and carrying a single gene mutation of the gene from 12 French centers. SETTINGS: This is a multicenter study. INTERVENTION: Detailed data on life habits (tobacco, alcohol, and nonsteroidal anti-inflammatory drugs), extraintestinal manifestations, and germline analysis were recorded. Complete endoscopic evaluation (colonoscopy and upper endoscopy) with chromoendoscopy was performed. RESULTS: Sixty-two patients were prospectively included (34 women (55%), mean age of 54, range 30-70 years). Thirty-two patients (52%) presented with colorectal polyps at colonoscopy. Of these patients with polyps, 15 (25%) had only adenomas, 8 (13%) had only hyperplastic polyps, 1 (1%) had sessile serrated adenomas, and 8 (13%) had adenomas and/or sessile serrated adenomas. We detected, in total, 29 adenomas with low-grade dysplasia, 5 adenomas with high-grade dysplasia, and 6 sessile serrated adenomas. Fourteen patients (23%) presented with a single adenoma, and 10 (16%) had 1 to 5 adenomas. No patient had more than 5 adenomas. At upper endoscopy, 3 had a limited number of fundic gland polyps; none had duodenal adenomas. The 2 main missense mutations c.1145G>A, p.Gly382Asp and c.494A>G, p.Tyr165Cys were associated with the development of colorectal adenomas/serrated polyps in these monoallelic carriers. LIMITATIONS: This study was limited by the small number of patients. CONCLUSIONS: This prospective study provides unique prospective data suggesting that monoallelic mutation carriers related to patients with polyposis show no colorectal polyposis and have very limited upper GI manifestations justifying an endoscopic follow-up. See Video Abstract at http://links.lww.com/DCR/A862.

Screening and surveillance in hereditary gastrointestinal cancers: Recommendations from the European Society of Digestive Oncology (ESDO) expert discussion at the 20th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona, June 2018.

Patients with hereditary gastrointestinal (GI) cancers represent a substantial fraction of the overall affected population. Although awareness for hereditary GI cancer syndromes is on the rise, identification of patients and measures of surveillance are often unclear in everyday clinical routine. Therefore, the European Society of Digestive Oncology expert discussion 2018 at the World Congress on Gastrointestinal Cancer focussed on screening and surveillance of hereditary colorectal, gastric and pancreatic cancers. An international panel of experts and opinion leaders developed the here presented recommendations based on published evidence and on profound clinical expertise to facilitate clinical routine in identification and caretaking of patients with familial GI cancers.

Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study.

INTRODUCTION: Hepatic arterial infusion chemotherapy (HAIC) is a treatment used for liver metastases (LM) of colorectal cancer (CRC). Because of its technical conditions, it has been used in only a few experienced centers in France. Our aim was to evaluate its feasibility, efficacy and tolerance in 4 centers. METHODS: Clinical, biological, and radiological data of patients treated with HAIC for unresectable LM from CRC in 4 institutions from October 2011 to January 2016 were retrospectively analyzed. RESULTS: Sixty-one patients with unresectable LM from CRC were included. Patients had previously received systemic chemotherapy in 95% of patients and 82.8% had previous oxaliplatin treatment. Oxaliplatin was administered using an intra-arterial route combined with intravenous (I.V.) Five-fluorouracil (5-FU) with leucovorin alone in 43.3% of patients, or combined with other I.V. chemotherapies or monoclonal antibodies in 56.7% of patients. Grade 3 to 4 clinical toxicities were reported in 16% of patients, including 9.8% of neurotoxicity, and Grade 3 to 4 biological toxicities were reported in 24.6% of patients including 22.2% with neutropenia. Catheter-related complications were observed in 31.1%. Tumor response rate in first- and second-line was 26.5% and third- and fourth-line was 11%. Median overall survival (OS) in first- and second-line was 13.5 months and third- and fourth-line was 8.3 months (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.39-1.12; P = .1729). Median progression-free survival (PFS) in first- and second-line was 9 months and third- and fourth-line were 6 months (HR, 0.53; 95% CI, 0.18-0.659; P = .0037). A secondary R0 resection was possible in 10 cases (16.4%) allowing a 2-year survival of 80%. CONCLUSION: These data confirm that in centers that recently developed HAIC using oxaliplatin, this treatment is feasible and has acceptable tolerance. The results, in terms of hepatic PFS, PFS, OS, and the rate of secondary resections of LM, are in the range of published data, and they confirm the interest of HAIC in patients in progression after multiple I.V.

Short article: Evaluation of O6-methylguanine-DNA methyltransferase as a predicting factor of response to temozolomide-based chemotherapy in well-differentiated metastatic pancreatic neuroendocrine tumors.

OBJECTIVE: Temozolomide (TMZ) is an alkylating agent frequently used in well-differentiated metastatic pancreatic neuroendocrine tumors (PNETs) with very variable responses. O-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose loss of expression has been suggested to be predictive of response to TMZ in various human tumors. We evaluated the predictive value of MGMT status, assessed by immunohistochemistry (IHC) and methylation-specific PCR (MS-PCR), in well-differentiated metastatic PNETs treated by a TMZ-based chemotherapy. PATIENTS AND METHODS: All patients with metastatic PNETs treated with TMZ-based chemotherapy between 2010 and 2016 in two academic centers, for whom the tumor samples were available, were included. Clinical data were collected and the MGMT status of the tumors was analyzed using MS-PCR and IHC. RESULTS: Twenty-two patients (nine men, median age 61 years) were included. The loss of MGMT protein expression detected by IHC was observed in 13 (59%) patients and MGMT promoter hypermethylation was detected by MS-PCR in three (15%) out of 20 interpretable cases. MGMT status did not correlate significantly with the best radiological response according to the Response Evaluation Criteria In Solid Tumors criteria or with progression-free survival. There was no correlation between MGMT protein expression and MGMT gene promoter methylation. CONCLUSION: These results indicate that a deficient MGMT status in PNETs, determined by loss of protein expression in IHC or by the presence of MGMT gene promoter methylation measured by MS-PCR, is not associated with a better response to TMZ-based chemotherapy and cannot be used as a predictive marker to lead treatment decisions.

Clinical, histological, and molecular risk factors for cancer recurrence in patients with stage II colon cancer.

INTRODUCTION: The assessment of risk factors of cancer recurrence in patients with stage II colon cancer (CC) is crucial. Our aim was to study the clinical, histological, and molecular features associated with 3-year disease-free survival in a series of consecutive patients with stage II CC treated in three regional digestive oncology centers. METHODS: Clinical and histological data of all patients after curative surgery for stage II CC, treated from 2001 until 2009, were collected retrospectively. Histological samples were obtained and tested prospectively for microsatellite instability using fluorescent PCR amplification. Cox proportional hazards regression models were used to calculate P values, hazard ratios (HRs), and 95% confidence intervals (CIs). RESULTS: Among 195 patients studied, 22 (11%) had disease recurrence during the 3-year period following diagnosis. On multivariate analysis, only low number of lymph nodes (HR=3.81, 95% CI: 1.19-12.19, P=0.02) and T4 status (HR=5.49, 95% CI: 1.06-28.43, P=0.04) were associated significantly with an increased risk of relapse. CONCLUSION: In this series of stage II CC patients, only T4 status and low number of lymph nodes were independent risk factors for poor 3-year disease-free survival, suggesting that patients with these features should be considered for adjuvant chemotherapy.

Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study.

BACKGROUND: Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02). CONCLUSION: This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC.

Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk.

To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's χ(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P<0.0001) cumulative effect of the at-risk alleles or genotypes with OR at 1.62 (CI: 1.10-2.37), 2.09 (CI: 1.43-3.07), 2.87 (CI: 1.76-4.70) and 3.88 (CI: 1.72-8.76) for 1, 2, 3 and at least 4 at-risk alleles, respectively, and OR at 1.71 (CI: 1.18-2.46), 2.29 (CI: 1.55-3.38) and 6.21 (CI: 2.67-14.42) for 1, 2 and 3 at-risk genotypes, respectively. Combination of SNPs may therefore explain a fraction of clinical situations suggestive of an increased risk for CRC.

Evaluation of the colorectal cancer risk conferred by rare UNC5C alleles.

AIM: To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer (CRC). METHODS: We screened patients with familial CRC forms as well as patients with sporadic CRCs. In a first time, we analyzed exon 11 of the UNC5C gene in 120 unrelated patients with suspected hereditary CRC, 58 patients with suspected Lynch-associated cancer or polyposis, and 132 index cases of Lynch syndrome families with a characterized mutation in a DNA mismatch repair (MMR). Next, 1023 patients with sporadic CRC and 1121 healthy individuals were screened for the variants identified in patients with familial cancer. RESULTS: Of 120 patients with familial CRC of unknown etiology, one carried the previously reported mis-sense mutation p.Arg603Cys (R603C) and another exhibited the unreported variant of unknown significance p.Thr617Ile (T617I). The p.Ala628Lys (A628K) mutation previously described as the main UNC5C risk variant for familial CRC was not detected in any cases of familial CRC of unknown etiology, but was present in a patient with familial gastric cancer and in two Lynch syndrome patients in co-occurrence with MMR mutations. A statistically non-significant increase in cancer risk was identified in familial CRC and/or other Lynch-associated cancers (1/178 patients vs 2/1121 healthy controls, OR = 3.2, 95%CI: 0.29-35.05, P = 0.348) and in sporadic CRCs (4/1023 patients vs 2/1121 healthy controls, OR = 2.2, 95%CI: 0.40-12.02, P = 0.364). CONCLUSION: We confirm that UNC5C mutations are very rare in familial and sporadic CRCs, but further investigations are needed to justify routine UNC5C testing for diagnostic purposes.

Detection, isolation, and characterization of alpha-fetoprotein-specific T cell populations and clones using MHC class I multimer magnetic sorting.

alpha-fetoprotein (AFP) is a fetal protein specifically reexpressed in 50% of hepatocellular carcinomas. This protein could serve as a tumor-associated antigen for immunotherapy purpose. The aim of our work was to analyze the presence of AFP-specific T cell populations in peripheral blood mononuclear cells (PBMCs) from cirrhotic patients with or without hepatocellular carcinoma. Using peptide-major histocompatibility complex class I multimers, AFP-specific populations corresponding to 3 previously described human leukocyte antigen (HLA)-A*0201 major histocompatibility complex class I epitopes (AFP137, AFP158, and AFP325) were sorted magnetically from CD8 positive cells without prior stimulation with the target antigen. T cell populations specific for 1 peptide (AFP158) were frequent, whereas populations corresponding to peptide AFP137 were rare and absent for peptide AFP325. We also isolated and fully characterized T cell clones specific for AFP137 and AFP158 peptides. We show that these clones can be used to monitor dendritic cell loading with peptides and could be useful for future immunotherapy protocols.