Serrated polyps: innocent or guilty? / Pólipos serrados: ¿inocente o culpable?

ABSTRACT Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives.

RESUMEN Las lesiones serradas representan un grupo de lesiones con diferentes características genéticas y biológicas que provocan importantes repercusiones clínicas. Se identifican tres tipos de lesiones serradas: adenomas hiperplásicos, sésiles (con y sin displasia) y adenomas serrados tradicionales. Estas lesiones se reconocen actualmente como lesiones precancerosas.El proceso carcinogénico de las lesiones serradas sigue una vía que incluye: alteraciones relativas a la activación del mitógeno y de la proteína quinasa reguladora de la señal extracelular de otras quinasas intracelulares (MAPK-ERK), inhibición de la apoptosis e hipermetilación del ADN e inestabilidad microsatelital. Al igual que en el caso de los pólipos adenomatosos, los factores de riesgo de las lesiones serradas son factores ambientales, relacionados con el estilo de vida y la dieta. El riesgo cancerígeno aumenta con el consumo excesivo de alcohol, la obesidad y la ingesta deficiente de folatos. Cuando se diagnostica un número elevado de pólipos colorrectales con arquitectura serrada, puede considerarse como síndrome de poliposis serrada (SPS). Según las guías más recientes de la ESGE, los criterios diagnósticos del SPS, son: al menos 5 pólipos resecados proximalmente al colon sigmoides, 2 de los cuales> 10 mm, o > 20 lesiones serradas de cualquier tamaño distribuidas en todo el colon. Esta condición presenta un alto riesgo de CCR personal y/o familiar, por lo que debe realizarse una colonoscopia de cribado periódica en estos pacientes y en sus familiares de primer grado.

DNA methylation variations in familial female and male breast cancer.

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. The aim of the present study was to examine the global DNA methylation profiles of patients with BC to identify differences between familial female breast cancer (FBC) and MBC, and according to BRCA1, BRCA2 or BRCAX mutation status. The genomic DNA of formalin-fixed paraffin-embedded tissues from 17 women and 7 men with BC was subjected to methylated DNA immunoprecipitation and hybridized on human promoter microarrays. The comparison between FBC and MBC revealed 2,846 significant differentially methylated regions corresponding to 2,486 annotated genes. Gene Ontology enrichment analysis revealed molecular function terms, such as the GTPase superfamily genes (particularly the GTPase Rho GAP/GEF and GTPase RAB), and cellular component terms associated with cytoskeletal architecture, such as 'cytoskeletal part', 'keratin filament' and 'intermediate filament'. When only FBC was considered, several cancer-associated pathways were among the most enriched KEGG pathways of differentially methylated genes when the BRCA2 group was compared with the BRCAX or BRCA1+BRCAX groups. The comparison between the BRCA1 and BRCA2+BRCAX groups comprised the molecular function term 'cytoskeletal protein binding'. Finally, the functional annotation of differentially methylated genes between the BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were associated with GTPase activity. In conclusion, to the best of our knowledge, the present study was the first to compare the global DNA methylation profile of familial FBC and MBC. The results may provide useful insights into the epigenomic subtyping of BC and shed light on a possible novel molecular mechanism underlying BC carcinogenesis.

Serrated polyps: innocent or guilty?

Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives.

Differential Diagnosis of Small Cell Carcinoma of the Ovary or Ovarian Metastases of Small Cell Carcinoma of the Lung: A Case Report and Review of the Literature.

Small cell tumors arise from the neuroendocrine cell system and they are most frequently found in the lung (SCLC). Small cell tumor could occasionally arise in other body sites, such as the cervix, prostate, gastrointestinal tract, and very rarely from other sites. Metastatic SCLC patients present with metastatic disease in 80% of cases, and the metastases typically are reported in brain, liver, lung, and bone; they rarely could be found in the ovary. Differently, primitive small cell carcinoma of the ovary of pulmonary type is a rare and highly aggressive tumor arising from the ovarian cells; no suitable treatment strategy has been established yet. In this paper, we talk about a 72-year-old woman who presented with abdominal bleeding and a large mass in her pelvic region. A primary ovarian carcinoma was suspected, and she underwent hysterectomy with laparoscopic surgery and bilateral oophorectomy, lymph node resection, omentectomy, complementary appendix and sigmoid resection. The postoperative pathologic diagnosis was a differential diagnosis between small cell ovarian carcinoma of the pulmonary type and metastasis of SCLC.

A Rare Complex BRAF Mutation Involving Codon V600 and K601 in Primary Cutaneous Melanoma: Case Report.

BRAF is one of the most common mutated kinases detected in human cancer, particularly in cases of primary cutaneous melanomas (PCM). Mutations of the BRAF proto-oncogene, at the p.V600 codon, has been detected in more than 50% of primary and metastatic melanoma cells in clinical samples. In addition to the most frequent BRAF p.V600E mutation, corresponding to the single base pair substitution c.1799T>A, rarer mutations, within and outside the V600 codon, have been described. Expectedly, BRAF and MEK inhibitors (or their combination) have been poorly explored as potential therapeutic strategies in metastatic melanomas harboring this rare mutation. By using a set of sequencing techniques and immunohistochemistry, this work reports the genomic and clinical features of two melanoma patients showing a rare complex mutation affecting codon V600 and K601 of the BRAF gene, leading to a V600E2; K601I change. Specifically, these two patients show a distinct clinical behavior and significantly differ in their responses to BRAF and MEK inhibitors. Indeed, although this treatment has proven to be effective and safe in both cases, the observed variability between the two patients resulted as a direct consequence of the baseline extent of brain involvement, intracranial treatment failure as well as on the PTEN status.

A Multifocal Glioneuronal Tumor with RGNT-Like Morphology Occupying the Supratentorial Ventricular System and Infiltrating the Brain Parenchyma.

BACKGROUND: Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent evidence based on molecular data suggest that low-grade glioneuronal tumors (GNT) involving the septum pellucidum and the lateral ventricles, with either dysembryoplastic neuroepithelial tumor-like or RGNT-like features, may belong to a neuropathologic entity distinct from cortical dysembryoplastic neuroepithelial tumor and "typical" fourth ventricle RGNT, respectively. Given their rarity, the classification of these neoplasms is still uncertain and their clinicopathological and radiological aspects are only partially known. CASE DESCRIPTION: A 24-year-old male presented a GNT with RGNT-like morphological features centered in the septum pellucidum with multifocal masses occupying the lateral ventricles and the third ventricle with extraventricular infiltration of the frontal lobe. The patient underwent subtotal resection and 4 years follow-up. The clinicopathological and radiological features of the neoplasm are discussed. CONCLUSIONS: Advanced magnetic resonance imaging (magnetic resonance spectroscopy and perfusion-weighted imaging) may provide valuable information in the differential diagnosis between rare GNTs and other more frequent intraventricular neoplasms. In the present case, the enhancing remnant portion of the tumor showed remarkable contrast enhancement variability during the follow-up with slow in situ progression. However, available data suggest that spontaneous contrast enhancement "fluctuations" over time in RGNT may not represent a reliable indicator of tumor behavior.

Diagnosis of Mixed Adenoneuroendocrine Carcinoma (MANEC) after Neoadjuvant Chemotherapy for Pancreatic and Gastric Adenocarcinoma: Two Case Reports and a Review of the Literature.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract involving both epithelial and neuroendocrine (NE) components, each of which represents at least 30% of the tumor. Because of the low frequency of this histotype, only a few cases have been described. In this report we discuss two cases treated with neoadjuvant chemotherapy: a pancreatic adenocarcinoma and a gastric adenocarcinoma. The histopathological specimens examined after surgery showed an additional NE component with a possible indication of the MANEC histotype. We hypothesize two possible explanations: tumor NE cells are more chemo-resistant than adenocarcinoma cells, and cytotoxic injury induces NE differentiation in tumor cells. The clinical significance and prognostic value of endocrine differentiation, however, remain controversial issues.

Integrated Diagnostic Model That Incorporates Epstein-Barr Virus DNA, Imaging, and Nasal Endoscopy to Stratify Primary Tumor and Lymph Nodes in a Patient with N1 Nasopharyngeal Carcinoma: Multidisciplinary Management.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC. In March 2016, a 54-year-old male with NPC cT1 cN2 cM0, stage III (8th edition of American Joint Committee on Cancer (AJCC) staging system) underwent to a two-step treatment: induction chemotherapy by TPF regimen (docetaxel, cisplatin, 5-fluorouracil), followed by concomitant chemoradiotherapy (weekly cisplatin). The quantity of free plasma EBV-DNA can be related to the disease stage, and the detection of EBV-DNA during follow-up can be predictive of distant metastases. Especially, either plasma or serum EBV-DNA titer is estimated to reflect tumor volume. Biologically, such EBV-DNA reflects reproduced or released DNA from dead or dying tumor cells. On the other hand, EBV-specific DNA released as exosome may reflect the biological feature of the alive NPC tumor cell. The follow-up is ongoing after 21 months from a complete response.

Dark sputum: An atypical presentation of primary pulmonary malignant melanoma.

Primary melanoma of the lung is an extremely rare clinical entity. We found only 32 cases reported in literature, and in two of these multiple brain metastases were present. We describe a case of primary lung melanoma with brain and skin metastases that presented with an initial clinical diagnosis of pneumonia. A 55-year-old white man presented with cough productive of dark sputum and fever. A chest x-ray showed a right lung infiltration. After failure to respond to usual treatment for pneumonia, bronchoscopy examination and CT scan revealed a right pulmonary mass. The CT-guided biopsy confirmed a diagnosis of malignant melanoma. The primary lung origin of the tumor was demonstrated by the characteristic junctional pattern of melanoma cells. Further evaluation revealed metastases in the brain and in skin. Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease.

Clear cell thymic carcinoma: a case report.

Clear cell thymic carcinoma is a rare and invasive tumor of the mediastinum for which there are no uniform treatment guidelines. The combination of carboplatin plus paclitaxel seems to be the most effective regimen for this disease. We report a case of locally advanced clear cell thymic carcinoma treated with this schedule, in which we observed a relevant and rapid tumor shrinkage.

Primary osteosarcoma of the breast: a case report.

Introduction. Primary osteosarcoma of the breast is a rare soft-tissue form of osteosarcoma without involvement of the skeletal system. Due to the rarity of the disease, its clinical features and optimal treatment remain unclear. Case Presentation. This case report deals with a 62-year-old woman with pure osteosarcoma of the breast. Conclusions. The prognosis of primary osteosarcoma of the breast is poor. Recurrence is frequent, and it is often associated with haematogenous spread of the disease to the lung. Treatment follows the model of sarcomas affecting other locations and must be planned in a multidisciplinary fashion. Adjuvant chemotherapy should be considered for patients with tumors showing aggressive features.

[Sporadic case of desmoid tumor in outcomes of lombotomic nephrectomy]. / Un caso raro di lesione desmoide in esiti di nefrectomia con accesso lombotomico.

UNLABELLED: The desmoid tumor is a rare tumor with an incidence of 2-4 cases per million people each year, and represents 0.03% of all cancers. The tumor is composed of fibrous tissue that produces masses of well-differentiated hard elastic consistency. According to their site of onset, the desmoid tumors are classified in abdominal, intra-abdominal, and extra-abdominal. The abdominal cases develop inside the abdominal muscles of the abdominal wall upright, especially in women in their 2nd - 4th decade of life, particularly in those who have been pregnant. METHODS: A 66-year-old patient underwent nephrectomy in 2006 for the detection of a massive tumor in the right kidney (EI: pT1bNx). The patient came to our observation for the radiological tracking (CT) of a solid lesion of 4 cm below the right arch, 2 years after surgery. For this reason it was decided to refer the patient to a series of percutaneous biopsies. The report describes a histologic lesion of fibromatosis. After one year a new CT exam showed a significant increase of the size of the lesion, with a diameter of 11.6 x 7.9 cm, and abdominal involvement to ascending colon. Given the discrepancy between the CT data and the histological report, it was decided to refer the patient to a lombotomic exploration and the subsequent removal of the lesion, which appeared of hard, elastic consistency and well capsulated. The final histology test confirmed the fibromatosis lesion. CONCLUSIONS: The desmoid tumor is a rare tumor characterized by the proliferation of fibrotic tissue. The tumor is composed of well-differentiated fibrous tissue and has a hard-elastic consistency. Regarding the development of dermoid tumors, several risk factors were identified, including extra-abdominal fibromatosis, genetic factors, endocrine factors. Other causes may arise from trauma or abdominal injury in surgical outcomes of appendectomy, laparotomy and other surgical scars (scar fibromatosis) or genetic predisposing factors. The surgical resection of dermoid tumors should be the therapy of choice, complete and radical, to cover the possible excision of a wide margin of surrounding structures concerned, and those arrangements should ensure a low rate of relapse. However, in cases of inoperable cancer due to extension, anti-estrogen therapy may have an important therapeutic and well-tolerated effect, besides being relatively non-toxic, even at high doses. A close follow-up is indicated, however, and warmly recommended.

Preinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid).

Improved colonoscopy is revealing precancerous lesions that were frequently missed in the past, and ∼30% of those detected today have nonpolypoid morphologies ranging from slightly raised to depressed. To characterize these lesions molecularly, we assessed transcription of 23,768 genes in 42 precancerous lesions (25 slightly elevated nonpolypoid and 17 pedunculated polypoid), each with corresponding samples of normal mucosa. Nonpolypoid versus polypoid morphology explained most gene expression variance among samples; histology, size, and degree of dysplasia were also linked to specific patterns. Expression changes in polypoid lesions frequently affected cell-cycling pathways, whereas cell-survival dysregulation predominated in nonpolypoid lesions. The latter also displayed fewer and less dramatic expression changes than polypoid lesions. Paradigmatic of this trend was progressive loss through the normal > nonpolypoid > polypoid > cancer sequence of TMIGD1 mRNA and protein. This finding, along with TMIGD1 protein expression patterns in tissues and cell lines, suggests that TMIGD1 might be associated with intestinal-cell differentiation. We conclude that molecular dysregulation in slightly elevated, nonpolypoid, precancerous colorectal lesions may be somewhat less severe than that observed in classic adenomatous polyps.

Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis.

BACKGROUND: K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. METHODS: Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. RESULTS: Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN >or= 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN >or= 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively). CONCLUSION: FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.

Cutaneous epithelioid malignant schwannoma: review of the literature and case report.

A case of malignant epithelioid schwannoma in the skin is reported. This was a rare variant of a malignant tumour that arose on the back of a 35-year-old male without neurofibromatosis. Clinically the nodule appeared to be a benign cyst but as it was painful it was decided to remove it. Ultrastructural and immunohistochemical features of the lesion were consistent with those of malignant epithelioid schwannoma so a radical excision was performed. Most ordinary malignant schwannoma are located in the deep soft tissue of the proximal portions of the upper and lower extremities and trunk; to the best of our knowledge only 26 cases of malignant epithelioid schwannoma in the skin and subcutis have been described in the literature. For the 14 male and 12 female patients reviewed, the median age was 43 years (range 19-84). Upper extremities were the most common sites (10 of 26). Seven patients developed local recurrences and four developed metastases: two to lung, one to lung and lymph node, and one to lung, liver and brain. All patients with local recurrence and all except one who developed metastases did not undergo wide local excision. We can conclude that malignant epithelioid schwannoma in the skin and subcutis is eminently curable if treated with wide local excision.

Epidermal growth factor receptor gene promoter methylation in primary colorectal tumors and corresponding metastatic sites: a new perspective for an "old" therapeutic target.

OBJECTIVE: To clarify the role of epidermal growth factor receptor (EGFR) promoter methylation in primary colorectal cancers and corresponding metastases and its relationship to EGFR expression. STUDY DESIGN: Formalin-fixed tumor samples (primary site and metastasis)from colorectal cancer patients were analyzed for EGFR promoter methylation and EGFR immunohistochemistry expression. RESULTS: Among the 63 assessable patients, 25 cases (39.7%) showed EGFR promoter methylation. Forty-two primary colorectal tumors and corresponding metastases were available for paired analysis of EGFR methylation status. EGFR methylation status of the primary tumor was in accordance with that of metastasis in 29 patients (69%). In contrast, 7 patients (50%) with EGFR promoter methylation in the primary tumor showed unmethylated EGFR in metastasis, and 6 metastases (46%) showed EGFR promoter hypermethylation derived from unmethylated EGFR primary tumors. Lack of EGFR protein expression was observed in 8 EGFR promoter methylated primary tumors (44%) and in 7 EGFR promoter methylated metastatic sites (44%). CONCLUSION: EGFR promoter hypermethylation does not seem to represent a rare event in colorectal cancer and may be present differently in different tumor sites. These findings may be relevant to further studies investigating the role of EGFR in colorectal cancer patients.

Isolation and characterization of mesenchymal cells from human fetal membranes.

Bone marrow (BM) multipotent mesenchymal stromal cells (MSCs) present with multipotent differentiation potential and immunomodulatory properties. As an alternative to bone marrow, we have examined fetal membranes, amnion and chorion, of term human placenta as a potential source of multipotent MSCs. Here we show that amnion mesenchymal cells (AMCs) and chorion mesenchymal cells (CMCs), isolated by mechanical separation and subsequent enzymatic digestion, demonstrate plastic adherence and fibroblast-like morphology and are able to form colonies that could be expanded for at least 15 passages. By FACS analysis, AMCs and CMCs were shown to be phenotypically similar to BM-MSCs and, when cultured in differentiation media, they demonstrated high morphogenetic plasticity by differentiating into osteocytes, chondrocytes and adipocytes. In an attempt to isolate cells with MSC characteristics from human fetal membranes, AMCs and CMCs expressing CD271 were enriched by immunomagnetic isolation and were demonstrated to possess higher clonogenic and osteogenic differentiation potential than CD271-depleted fractions. Based on these findings, amnion and chorion can be considered as a novel and convenient source of adult MSCs.

Nuclear factor-kB tumor expression predicts response and survival in irinotecan-refractory metastatic colorectal cancer treated with cetuximab-irinotecan therapy.

PURPOSE: NF-kB expression has been shown to be responsible for resistance to antineoplastic agents and it also plays a part in the activation of the epidermal growth factor receptor downstream signaling pathway in colorectal tumors. The aim of our analysis was to investigate a correlation between NF-kB expression, response rate, time to progression, and survival in advanced colorectal cancer patients receiving cetuximab and irinotecan. PATIENTS AND METHODS: We analyzed retrospectively the immunoreactivity for NF-kB in irinotecan-refractory patients receiving cetuximab and irinotecan. Results Seventy-six patients were analyzed. Cetuximab and irinotecan were administered as second-line chemotherapy in 19 patients and after > or = two lines of chemotherapy in the remaining 57 patients. We observed a partial response (PR) in 16 patients for an overall response rate of 24%. Thirty-two patients (48%) experienced progressive disease; median time to progression (TTP) was 3.6 months and median overall survival was 10.3 months. NF-kB was positive in 46 patients (60%). All main clinical characteristics were well balanced between NF-kB-positive and NF-kB-negative patients. The response rate was 10% (four PRs) versus 48% (12 PRs; P = .0007) in NF-kB-positive and NF-kB-negative tumors, respectively. Median TTP in NF-kB-positive patients was 3 v 6.4 months in the remaining patients (P = .021). Median overall survival was 9.5 v 15.8 months for NF-kB-positive and NF-kB-negative patients, respectively (P = .036) CONCLUSION: The difference in median TTP, overall survival, and response rate seem to confirm that NF-kB may play a crucial role in predicting the efficacy of cetuximab and irinotecan in advanced colorectal tumors.