IGF1R acts as a cancer-promoting factor in the tumor microenvironment facilitating lung metastasis implantation and progression.

Given the long-term ineffectiveness of current therapies and late-stage diagnoses, lung cancer is a leading cause of malignant diseases. Tumor progression is influenced by cancer cell interactions with the tumor microenvironment (TME). Insulin-like growth factor 1 receptor (IGF1R) was reported to affect the TME; however, the role of IGF1R in lung TME has not been investigated. First, we assessed IGF1R genomic alterations and expression in NSCLC patient tissue samples, as well as IGF1R serum levels. Next, we performed tumor heterotopic transplantation and pulmonary metastases in IGF1R-deficient mice using melanoma and Lewis lung carcinoma (LLC) cells. Herein we report increased amplification and mRNA expression, as well as increased protein expression (IGF1R/p-IGF1R) and IGF1R levels in tumor samples and serum from NSCLC patients, respectively. Moreover, IGF1R deficiency in mice reduced tumor growth, proliferation, inflammation and vascularization, and increased apoptosis after tumor heterotopic transplantation. Following induction of lung metastasis, IGF1R-deficient lungs also demonstrated a reduced tumor burden, and decreased expression of tumor progression markers, p-IGF1R and p-ERK1/2. Additionally, IGF1R-deficient lungs showed increased apoptosis and diminished proliferation, vascularization, EMT and fibrosis, along with attenuated inflammation and immunosuppression. Accordingly, IGF1R deficiency decreased expression of p-IGF1R in blood vessels, fibroblasts, tumor-associated macrophages and FOXP3+ tumor-infiltrating lymphocytes. Our results demonstrate that IGF1R promotes metastatic tumor initiation and progression in lung TME. Furthermore, our research indicates that IGF1R could be a potential biomarker for early prediction of drug response and clinical evolution in NSCLC patients.

Cytogenetic and immunohistochemical study of 42 pigmented microcystic chromophobe renal cell carcinoma (PMChRCC).

Pigmented microcystic chromophobe renal cell carcinoma (PMChRCC) is a recently described morphologic variant of ChRCC. We have identified 42 cases in 40 patients in the last 24 years. We have investigated their clinical, morphologic, immunohistochemical, and cytogenetic features. Chromosomal abnormalities of chromosomes 7 and 17 were evaluated by automated dual-color silver-enhanced in situ hybridization on paraffin-embedded tissue. Chromosomal imbalance was defined on the basis of changes in both chromosomal index and signal distribution. The main age was 60.20 years, being 34 males and 6 women. The mean tumor diameter was 4.84 cm, with 39 intrarenal tumors. Grossly, the tumors were solid with a brown dark colored. Microscopically, tumors consisted of pale and eosinophilic cells arranged in microcysts or microalveolar in a cribriform pattern; there were microcalcifications and a dark brown pigment, mostly extracellular. One case showed sarcomatoid transformation. All tumors were positive for epithelial membrane antigen (EMA), Claudin 7, and E-cadherin. Monosomy of 7 and 17 chromosomes was present in 1/36 cases and 2/37 cases, respectively. Polysomy of chromosome 7 and 17 was found in 26/36 cases and in 4/37, respectively. With a median follow-up of 74.05 months, 37 patients were alive without disease and two were alive with disease progression. PMChRCCs expand the morphologic spectrum of the ChRCC with an unusual immunohistochemical profile. Cytogenetically, they showed monosomy to chromosome (CHR) 17 as other ChRCCs and polysomy of CHR 7 infrequent to ChRCCs. We present the probably largest series of PMCRCC, confirming their low aggressive behavior, with exceptional sarcomatoid transformation and distant metastases.

A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse gastric cancer.

Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15-50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDGC harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of gastric adenocarcinoma and some of her relatives were tested. Study of the entire CDH1 gene, including intron-exon boundaries, by PCR and sequencing and immunohistochemical determination of the expression of E-cadherin were performed. A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC, p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a premature stop codon giving rise to a truncated protein that leads to a pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the proband's tumor but normal in tumor cells of great-uncle. After these results, the sister underwent prophylactic total gastrectomy, and the nephew is under annual endoscopic surveillance. Personal or familial history of diffuse gastric cancer, above all at young age, should encourage CDH1 genetic testing. In this sense, the review of the criteria and the addition in the last guideline of the recommendation: "other families in which genetic testing may also be considered" broadens the number of individuals at risk detected. Since there are not reliable methods for early detection, DGC is usually diagnosed at an advanced stage and consequently associated with a poorer outcome. Thus, CDH1 mutations detection contributes to an improvement in diagnosis and therapeutic intervention.

Long-term oncologic results in cancer of the rectum treated by preoperative chemoradiotherapy and surgery: An analysis of 500 cases.

BACKGROUND: The standard treatment for locally advanced cancer of the rectum (LACR) and selective cases of stage IV disease is preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Despite reductions in local recurrence, disease-free survival (DSF) has remained stable in recent years. OBJECTIVE: The objective of this study is to analyze patterns of recurrence, long-term survival and prognostic factors in a program of neoadjuvant CRT and surgery in LACR. METHODS: Between January 1992 and December 2011, 446 patients with LACR and 54 patients (with single metastases) were treated with pre-operative long course CRT and surgery. Three hundred forty four (66.8%) anterior resections of the rectum and 123 (24.6%) abdomino-perineal resections were performed. RESULTS: With a mean follow-up of 70.06 months, local recurrence was 4.8% and distant recurrence 25.5%. No differences were found in the histopathologic prognostic factors across the three groups studied depending on distance (cm) from the analmargin. Involvement of the circumferential resection margin (CRM+) was significantly greater in tumors in the distal third of the rectum (8.5%; p = 0.04). 67 patients (13.4%) showed a complete pathologic response. DSF at 5 and 10 years was significantly lower in patients with tumors affecting the distal third as compared to the middle third of the rectum (61.9% vs. 57.7%; p = 0.04). Tumors at this distal location resulted in a significantly higher incidence of lung metastases (p = 0.016).

Resultados oncológicos a largo plazo en el cáncer de recto tratado con quimio-radioterapia preoperatoria y cirugía: análisis de 500 casos / Long-term oncologic results in cancer of the rectum treated by preoperative chemoradiotherapy and surgery: an analysis of 500 cases

ANTECEDENTES: el tratamiento del cáncer de recto localmente avanzado (CRLA) y de casos selectivos de estadio IV es la quimioradioterapia (QRT) preoperatoria seguida de la extirpación completa del meso-recto (ETM). A pesar de la reducción en la recurrencia local, la supervivencia libre de enfermedad (SLE) permanece estable en los últimos años. OBJETIVO: el objetivo de este trabajo es analizar el patrón de recidiva, supervivencia a largo plazo y los factores pronósticos en un programa de QRT neoadyuvante y cirugía en el CRLA. MÉTODOS: entre enero de 1992 y diciembre de 2011, 446 pacientes con CRLA y 54 pacientes (con metástasis únicas) fueron tratados con QRT preoperatoria de curso largo y cirugía. Se realizaron 344 (68,8%) resecciones anteriores de recto y 123 (24,6%) amputaciones abdominoperineales. RESULTADOS: con una mediana de seguimiento de 70,06 meses, la recurrencia local fue del 4,8% y a distancia del 25,5%. No se encontraron diferencias en los factores pronósticos histopatológicos entre los tres grupos estudiados dependiendo de la distancia (cm) al margen anal. La afectación del margen circunferencial (MCR+) fue significativamente mayor en el tercio distal (8,5%; p = 0,04). Sesenta y siete pacientes (13,4%) mostraron una respuesta patológica completa. La supervivencia libre de enfermedad a los 5 y 10 años fue significativamente menor en los tumores del tercio distal del recto que en los del tercio medio (61,9% y 57,7%; p = 0,04). En dicha localización se produjo una incidencia significativamente mayor de metástasis pulmonares (p = 0,016)

BACKGROUND: The standard treatment for locally advanced cancer of the rectum (LACR) and selective cases of stage IV disease is preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Despite reductions in local recurrence, disease-free survival (DSF) has remained stable in recent years. OBJECTIVE: The objective of this study is to analyze patterns of recurrence, long-term survival and prognostic factors in a program of neoadjuvant CRT and surgery in LACR. METHODS: Between January 1992 and December 2011, 446 patients with LACR and 54 patients (with single metastases) were treated with pre-operative long course CRT and surgery. Three hundred forty four (66.8%) anterior resections of the rectum and 123 (24.6%) abdomino-perineal resections were performed. RESULTS: With a mean follow-up of 70.06 months, local recurrence was 4.8% and distant recurrence 25.5%. No differences were found in the histopathologic prognostic factors across the three groups studied depending on distance (cm) from the anal margin. Involvement of the circumferential resection margin (CRM+) was significantly greater in tumors in the distal third of the rectum (8.5%; p = 0.04). 67 patients (13.4%) showed a complete pathologic response. DSF at 5 and 10 years was significantly lower in patients with tumors affecting the distal third as compared to the middle third of the rectum (61.9% vs. 57.7%; p = 0.04). Tumors at this distal location resulted in a significantly higher incidence of lung metastases (p = 0.016)

Tumor response assessment in locally advanced colon cancer after neoadjuvant chemotherapy.

BACKGROUND: Preoperative chemotherapy followed by radical surgery is a novel therapeutic approach for locally advanced colon cancer (LACC). Neoadjuvant strategies require highly accurate diagnostic tests for a proper selection of candidate patients, allowing a low risk of overtreatment. This paper assesses the radiological, metabolic and pathological findings induced by preoperative oxaliplatin and fluoropyrimidines-based chemotherapy in LACC. METHODS: Forty-four consecutive patients with a confirmed diagnosis of LACC who received neoadjuvant chemotherapy and colon surgery were included. All patients were staged at baseline and before surgery. Clinical diagnosis consisted of physical examination, endoscopy with biopsy and computed tomography (CT) scan. In selected cases, a positron emission tomography/CT (PET/CT) scan was also performed. Accuracy and correlations between CT scan findings and pathologic report was assayed for T stage, N stage and TN stage. This study is retrospective in design. RESULTS: After chemotherapy, a statistical significant tumor volume reduction of 62.5% was achieved by CT-scan (P<0.001; Wilcoxon test) and a 38.9% decrease of standard uptake value (SUVmax) was observed on PET/CT (P=0.004). No progressive disease was reported during neoadjuvant treatment. Accuracy for T and N classification was 62% and 87%, respectively. Accuracy for TN stage was 77%, with 13.6% and 9.1% of the patients being under or overstaged, respectively. Pathologic stage II and III disease was observed in 29/44 (65.9%) and 15/44 (34.1%) of the patients, respectively. Pathologic complete response was achieved in three patients. CONCLUSIONS: Oxaliplatin/fluorpyrimidine neoadjuvant chemotherapy induces major tumour shrinkage at both the pathological and radiological levels. The CT scan shows a high accuracy and a low overstaged rate in LACC patients treated by means of a neoadjuvant approach.

Prognosis factors for recurrence in patients with locally advanced rectal cancer preoperatively treated with chemoradiotherapy and adjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by total mesorectal excision has improved the outcome of locally advanced rectal carcinoma. OBJECTIVE: The aim of this study was to identify independent prognosis factors of disease recurrence in a group of patients treated with this approach. DESIGN AND PATIENTS: This study was retrospective in design. Data from patients with locally advanced rectal cancer who had completed treatment from 2000 to 2010 were reviewed. SETTINGS: The analysis was performed in a tertiary referral center. MAIN OUTCOME MEASURES: The primary outcomes measured were the recurrence risk factors. RESULTS: The cohort consisted of 228 patients; 69.3% of them were men, and median age was 59 years. Stage III rectal cancer was found in 64.9% of patients. The most frequently administered therapy was concurrent capecitabine, oxaliplatin, and 7-field radiotherapy, followed by 3-field radiotherapy and fluoropyrimidines. After a median follow-up of 49 months, 23.7% of the patients experienced disease recurrence: 2.6% had local recurrence, 21.1% had distant metastases, and 0.5% had both. Factors significantly correlated with recurrence risk in multivariate logistic regression were y-pathological stage (III vs I/II: OR = 2.51), tumor regression grade (1/2 vs 3+/4: OR = 3.34; 3 vs 3+/4: OR = 1.20), and low rectal location (OR = 2.36). The only independent prognosis factor for liver metastases was tumor regression grade (1/2 vs 3+/4: OR = 4.67; 3 vs 3+/4: OR = 1.41), whereas tumor regression grade (1-2 vs 3+/4: OR = 5.5; 3 vs 3+/4: OR = 1.84), low rectal location (OR = 3.23), and previous liver metastasis (OR = 7.73) predicted lung recurrence. LIMITATIONS: This is a single institutional experience, neoadjuvant combined therapy is not homogeneous, and the analysis has been performed in a retrospective manner. CONCLUSIONS: Patients with low third locally advanced rectal cancer with a poor response to neoadjuvant chemoradiotherapy (high y-pathological stage or low tumor regression grade) are at high risk of recurrence. Intense surveillance and the design of alternative therapeutic approaches aimed to lower the distant failure rate seem warranted.

Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer.

BACKGROUND: The immunoglobulin G1 (IgG(1)) monoclonal antibody (MoAb) Cetuximab is active in metastatic colorectal cancer (mCRC) as first or subsequent lines of therapy. Efficacy seems restricted to KRAS wild-type tumours. IgG(1) may also induce antibody dependent cell mediated citotoxicity (ADCC) by recruitment of immune effector cells. ADCC is influenced by Fc gamma receptor (FcγR) polymorphisms. We investigated the association of FcγR polymorphisms and disease control rate (DCR) in mCRC patients treated with chemotherapy plus Cetuximab. PATIENTS AND METHODS: Tumour tissues from 106 patients were screened for KRAS codon 12 and 13 mutations using a sensitive multiplex assay (DxS, Manchester, United Kingdom). NRAS (codons: 12, 13 and 61), PI3K (exon 20) and BRAF (exon 15) were analysed by direct sequencing. Fcγ RIIa and Fcγ RIIIa polymorphisms were genotyped by TaqMan assays. RESULTS: DCR was significantly higher in KRAS wild-type tumours (61% versus 39%, p = 0.049). In epidermal growth factor receptor (EGFR) downstream-mutated mCRC patients, those harbouring an FcγRIIa H/H genotype had a higher DCR than alternative genotypes (67% versus 33%, p = 0.017). By multivariate analysis, FcγRIIa-131H/H remained significantly correlated with DCR (p = 0.008). CONCLUSION: FcγR polymorphisms may play a role in the clinical efficacy of Cetuximab in EGFR downstream mutated mCRC patients. Further research into Cetuximab immune-based mechanisms in KRAS-mutated patients seems warranted.

Four-week neoadjuvant intensity-modulated radiation therapy with concurrent capecitabine and oxaliplatin in locally advanced rectal cancer patients: a validation phase II trial.

PURPOSE: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

Hamartoma gigante de glándulas de Brunner: diagnóstico y tratamiento endoscópico / Giant Brunner's gland hamartoma: diagnosis and endoscopic treatment

El hamartoma de glándulas de Brunner es una lesión polipoidea que histológicamente se caracteriza por una hiperplasia de estas glándulas junto con una proporción variable de músculo liso. Generalmente, cursa de forma silente y se comporta como una tumoración benigna. Ocasionalmente su crecimiento puede generar sintomatología digestiva que junto con la posibilidad de transformación maligna obliga a su resección tras realizar un amplio diagnóstico diferencial de masa duodenal. Tanto la clínica como los estudios radiológicos con frecuencia son inespecíficos y no permiten establecer su diagnóstico. El estudio endoscópico básico (gastroscopia) junto con una adecuada caracterización de la lesión mediante ecoendoscopia alta permiten establecer un diagnóstico de sospecha y determinar la mejor opción terapéutica (endoscópica o quirúrgica).Presentamos un caso de hamartoma de glándulas de Brunner gigante que debutó a modo de anemia ferropénica sin evidencia de sangrado. El estudio mediante ecoendoscopia alta permitió, tras adecuada caracterización de la lesión, su completa y segura resección endoscópica evitando un tratamiento quirúrgico más invasivo

Brunner's gland hamartoma is a polypoid lesion typically composed of an increased quantity of normal-appearing Brunner's glands, accompanied by a variable proportion of smooth muscle. Most of these masses are asymptomatic and behave as benign tumors. Occasionally tumoral growth can provoke gastrointestinal problems which, together with the possibility of malignant transformation, will require resection after a broad differential diagnosis has been made with solitary duodenal mass. Both clinical and radiographic studies are nonspecific and often do not allow diagnosis of these tumors. Basic endoscopic studies (upper endoscopy) with adequate characterization of the lesion by endoscopic ultrasound (EUS) can establish a high diagnostic suspicion and determine the best therapeutic option (endoscopy or surgery).We present a case of giant Brunner's gland hamartoma. The initial manifestation was iron-deficiency anemia with no evidence of bleeding. After adequate characterization of the lesion, EUS allowed complete and safe endoscopic resection, avoiding more invasive surgical treatment

[Giant Brunner's gland hamartoma: diagnosis and endoscopic treatment]. / Hamartoma gigante de glándulas de Brunner: diagnóstico y tratamiento endoscópico.

Brunner's gland hamartoma is a polypoid lesion typically composed of an increased quantity of normal-appearing Brunner's glands, accompanied by a variable proportion of smooth muscle. Most of these masses are asymptomatic and behave as benign tumors. Occasionally tumoral growth can provoke gastrointestinal problems which, together with the possibility of malignant transformation, will require resection after a broad differential diagnosis has been made with solitary duodenal mass. Both clinical and radiographic studies are nonspecific and often do not allow diagnosis of these tumors. Basic endoscopic studies (upper endoscopy) with adequate characterization of the lesion by endoscopic ultrasound (EUS) can establish a high diagnostic suspicion and determine the best therapeutic option (endoscopy or surgery). We present a case of giant Brunner's gland hamartoma. The initial manifestation was iron-deficiency anemia with no evidence of bleeding. After adequate characterization of the lesion, EUS allowed complete and safe endoscopic resection, avoiding more invasive surgical treatment.

A large gastric duplication (choristoma) in an adult mimicking a mucinous cystic tumor of the pancreas.

Gastric duplication represents a very rare entity in the adult population. Most of the symptoms are due to the presence of ectopic gastric mucosa (30-35% of cases), gastrointestinal bleeding or perforation or neoplasm formation. We report a case of gastric duplication in an adult mimicking a mucinous cystic neoplasm of the pancreas.

Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer.

PURPOSE: To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy. PATIENTS AND METHODS: Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m(2) twice daily Monday through Friday and oxaliplatin 60 mg/m(2) intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively. RESULTS: No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2. CONCLUSION: The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study.

A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients.

The benefit of postoperative adjuvant chemotherapy in patients with Dukes' B colorectal cancer is still uncertain and its routine use is not recommended. The five-year relapse rate is approximately 25-40% and the identification of patients at high risk of recurrence would represent an important strategy for the use of adjuvant chemotherapy. We retrospectively analyzed gene expression profiles in frozen tumor specimens from patients with Dukes' B colorectal cancer by using high density oligonucleotide microarrays. Our results show a subset of 48 genes differentially expressed with an associated probability <0.001 in the t-test. Another statistical procedure based on the Fisher criterion resulted in 11 genes able to separate both groups. We selected the 8 genes present in both subsets. The differential expression of five genes (CHD2, RPS5, ZNF148, BRI3 and MGC23401) in colon cancer progression was confirmed by real-time PCR in an independent set of patients of Dukes' B and C stages.

Fibroadenomas de mama con atipia o carcinoma en su interior: presentación de nuestra experiencia / Fibroadenomas of the breast with atypia or carcinoma in its interior: presentation of our experience

La presencia de atipia o carcinoma en un fibroadenoma es un hallazgo infrecuente. Se ha realizado un estudio retrospectivo de los archivos de nuestro centro desde enero de 1995 hasta junio de 2003. Se encontraron un total de 881 fibroadenomas con confirmación histológica, y siete de ellos con atipia o carcinoma asociados (dos carcinomas ductales in situ, dos carcinomas lobulillares in situ, y tres hiperplasias ductales con atipia). La edad media fue de 44 años (rango: 36-67). Cuatro de los siete fibroadenomas se presentaron como lesiones palpables que habían experimentado crecimiento, que correspondieron a los cuatro casos de carcinoma. Hallazgos mamográficos (tres casos): dos agrupaciones de microcalcificaciones y un nódulo bien delimitado. Hallazgos ecográficos (seis casos): cuatro nódulos ovoideos bien definidos, un nódulo con calcificaciones y un nódulo ovoideo bien definido de ecoestructura heterogénea. El diagnóstico inicial se realizó mediante biopsia escisional en 5 casos y mediante biopsia con aguja gruesa en otros dos casos. Los dos casos de biopsia con aguja gruesa tuvieron un primer resultado de fibroadenoma, pero la cirugía posterior demostró la presencia de carcinoma ductal in situ y un carcinoma lobulillar in situ. En conclusión se puede decir que los fibroadenomas con atipia o carcinoma pueden ser similares a los fibroadenomas habituales en mamografía y ecografía. Sin embargo, el crecimiento de un nódulo palpable, la presentación mamográfica como microcalcificaciones sospechosas o el hallazgo ecográfico de un nódulo heterogéneo, obligan a la realización de una biopsia escisional para un diagnóstico fiable

The pathological finding of atypia or carcinoma in a fibroadenoma is not frequent. We performed a retrospective study at our institution from January 1995 to June 2003. Seven cases with associated atypia or carcinoma (with histological confirmation) were found out of a total of 881 fibroadenomas. Two ductal carcinomas in situ (DCIS), two lobular carcinomas in situ (LCIS) and three ductal hyperplasias with atypia were found among the seven cases. Mean age was 44 years (range from 36 to 67 years). Four lesions were palpable and experienced growth, corresponding with the carcinoma cases. Mammographic findings (3 cases): Two groups of polymorphic microcalcifications and a well-defined ovoid nodule with heterogeneous echostructure. The initial diagnosis was done by excisional biopsy in five cases and by core needle biopsy in two other cases. The first result of the two cases of core biopsy was fibroadenoma, however subsequent surgery demonstrated the presence of DCIS and LCIS. In conclusion fibroadenomas with atypia or carcinoma may be similar to usual fibroadenomas in mammography and ultrasonography. However, growth of a palpable nodule, mammographic presentation as suspicious microcalcifications, or the ultrasonographic findings of heterogeneous nodule make it necessary to conduct an excisional biopsy for reliable diagnosis

Disminución de tamaño de un cáncer de mama tras biopsia con aguja gruesa / Reduction in breast tumor size after core needle biopsy

La biopsia de lesiones mamarias con aguja gruesa es una técnica diagnóstica muy difundida, que se acompaña de escasas complicaciones. Presentamos un caso de disminución del tamaño de un carcinoma ductal infiltrante tras la realización de una biopsia con aguja gruesa de calibre 14-G, que complicó la posterior localización con arpón metálico. Tras la escisión de la lesión, se comprobó una extensa necrosis del tumor, con zonas hemorrágicas. En la bibliografía revisada únicamente se han publicado dos casos similares, y ambos tras punciones con aguja fina (AU)

Loss of FHIT protein expression is related to high proliferation, low apoptosis and worse prognosis in non-small-cell lung cancer.

The fragile histidine triad (FHIT) gene, located at chromosome 3p14.2, is deleted in many solid tumors, including lung cancer. Its protein product is presumed to have tumor suppressor function. We investigated the incidence of loss of heterozygosity and loss of FHIT expression in a series of non-small-cell lung carcinomas and its correlation to apoptosis, proliferation index and prognosis. FHIT expression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissues from 54 squamous cell carcinomas (SCC) and 44 adenocarcinomas (AC) of the lung. DNA from frozen tumor and corresponding normal tissues were analyzed for allelic losses at two loci located internal (D3S1300, D3S1234) and three loci in flanking regions centromeric and telomeric (D3S1210, D3S1312, D3S1313) to the FHIT gene. Apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL). Proliferation index was determined with ki-67 and flow cytometric analysis. We correlated the results with tumor histology, prognosis and some immunohistochemical markers (p53, bcl-2, bax, c-myc, p21(waf1), cyclin-D1). FHIT expression was related to tumor histology: 52 of 54 (96.3%) SCC and 20 of 44 (45.5%) AC were negative for FHIT (P<0.0001). We found LOH at 3p14.2 in 67.8% of the 98 cases: 72.3% of SCC and 61.4% of AC. Loss of FHIT expression was associated with a higher proliferation index (ki-67, P=0.007; flow cytometry, P<0.004) and lower apoptotic index (P=0.018). LOH at FHIT gene were associated to a high proliferation (flow cytometry, P<0.001) and lower apoptotic level (P=0.043). The log-rank test demonstrated a significant inverse correlation (P=0.039) between loss of FHIT expression and patient survival. FHIT plays an important role in the development of non-small-cell lung cancer, particularly in SCC. Loss of FHIT protein is correlated with a high proliferation and low apoptotic index in tumor cells, and is an independent prognostic indicator for the clinical outcome in patients with these tumors.