RESUMO
Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases.
Assuntos
Adenocarcinoma/enzimologia , Neoplasias do Sistema Nervoso Central/enzimologia , Neoplasias Esofágicas/enzimologia , Junção Esofagogástrica/patologia , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/enzimologia , Amplificação de Genes , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
c-Met is a receptor tyrosine kinase shown to be overexpressed in malignant pleural mesothelioma (MPM). Whereas MET mutations have been identified in 3%-16% of MPMs, MET amplification has recently been reported in a single epithelioid MPM. We studied c-Met expression and MET amplification in a large MPM cohort and correlated results with morphologic and clinical features. We report the first case of MET amplification in sarcomatoid MPM. MPMs from surgical pathology files (1989-2014) were reviewed. c-Met immunohistochemistry was performed. Staining intensity and distribution were multiplied (H-score). Staining localization (cytoplasmic and/or membranous) was noted. Fluorescence in situ hybridization was performed using probes for MET and centromere 7. One hundred forty-nine patients (median age, 68.0years; interquartile range, 61-75) had epithelioid (n=97), biphasic (n=18), or sarcomatoid (n=34) MPM. Median follow-up was 10.1months (range, 0.1-222.5). One hundred thirty patients died of disease; 2 were alive with disease. c-Met was expressed in 147 MPMs. c-Met staining intensity, distribution, and H-score differed among the histologic subtypes (P=.015; P=.0001, and P=.0005, respectively), but none were predictive of survival. Epithelioid subtype had greater c-Met expression. MET amplification was identified in 1 sarcomatoid MPM and MET duplication in 1 epithelioid MPM; both had poor outcomes. Chromosome 7 aneusomy was observed in 54 of 144 (37.5%) MPMs and associated with decreased overall survival in sarcomatoid MPMs (hazard ratio=2.81; 95% confidence interval, 1.21-6.51; P=.01). In conclusion, c-Met is expressed in MPM, with significant differences in expression among histologic subtypes. MET amplification is a rare event in MPM, making it an unlikely common pathogenesis for c-Met expression.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Idoso , Feminino , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente , Masculino , Mesotelioma Maligno , Pessoa de Meia-Idade , Prognóstico , Sarcoma/diagnóstico , Sarcoma/metabolismoAssuntos
Implantes de Mama/efeitos adversos , Neoplasias da Mama/cirurgia , Linfoma Anaplásico de Células Grandes/classificação , Linfoma Anaplásico de Células Grandes/genética , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Adulto , Idoso , Neoplasias da Mama/complicações , Feminino , Rearranjo Gênico , Humanos , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors' knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance. METHODS: Patients with untreated EACs (N = 673) were analyzed for HER2 amplification and polysomy 17 by fluorescence in situ hybridization in parallel with immunohistochemistry (IHC) (IHC scores of 0-1+, 2+, and 3+). Amplification was defined as HER2/CEP17 ≥ 2. HER3 expression by IHC was analyzed in randomly selected cases (n = 224). IHC and fluorescence in situ hybridization results were compared using least squares linear regression. RESULTS: Overall, 17% of the EACs (116 of 673 EACs) were HER2-amplified with an amplification frequency that was highest among IHC3+ cases (89%) and declined among IHC2+ cases (13%) and IHC0 to IHC1+ cases (4%). Among HER2-amplified cases, the level of amplification increased linearly with HER2 membranous expression (HER2/CEP17 ratio: 7.9 in IHC3+ and 5.5 in IHC2+ vs 2.8 in IHC0 to IHC1+ [P < .0001]), with 14% of amplified tumors demonstrating absent/faint expression (IHC0 to IHC1+). Polysomy 17 was not found to be associated with HER2 expression. Cytoplasmic HER3 expression was detected in 87% of tumors (195 of 224 tumors) and was found to be significantly associated with better differentiation (P < .0001). Stepwise increases in HER3 expression were associated with higher HER2 expression levels (P = .0019). CONCLUSIONS: Levels of HER2 protein expression and amplification were found to be linearly associated and highly concordant. Among amplified tumors with absent/faint expression, the level of amplification was low. Frequent expression of HER3 suggests its relevance as a therapeutic target, and its significant association with HER2 supports ongoing efforts to inhibit HER2/HER3 in patients with EAC.
Assuntos
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Amplificação de Genes , Receptor ErbB-2/genética , Receptor ErbB-3/análise , Adenocarcinoma/química , Adenocarcinoma/patologia , Idoso , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/análiseAssuntos
Fosfatases de Especificidade Dupla/genética , Linfoma Anaplásico de Células Grandes/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Biópsia , Dinamarca/epidemiologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Linfoma Anaplásico de Células Grandes/mortalidade , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/análise , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores Proteína Tirosina Quinases/análise , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Our purpose was to evaluate the prognostic impact of pathologically confirmed esophageal adenosquamous carcinoma (ASC) and its association with HER2 status and clinicopathologic characteristics. METHODS: Among 796 patients with esophageal or gastroesophageal junction adenocarcinoma who underwent curative resection, surgical pathology reports were reviewed, and suspected ASC was confirmed utilizing p63 and CK5/6 immunostaining. HER2 status was determined using immunohistochemistry and fluorescence in situ hybridization. Cox models were used to assess the impact of ASC on disease-specific survival and overall survival. RESULTS: Overall, 2.0% (16/796) of patients had esophageal ASC, mostly demonstrating a close intermingling of squamous and adenocarcinoma cells within the same tumor. The percentage of squamous versus adenocarcinoma cells in the primary was generally recapitulated in nodal metastases, and intrapatient internodal heterogeneity was uncommon. Patients with esophageal ASC were statistically significantly more likely to be female (vs. male), have normal (vs. excess) body mass index, and harbor HER2-negative (vs. positive) tumors, as compared with patients with adenocarcinoma only. No ASC tumor was HER2-positive as compared with 16% of adenocarcinoma only tumors (P=0.018). Compared with patients with adenocarcinoma only, those with ASC demonstrated profoundly worse disease-specific survival (5-year event-free rate, 34% vs. 6%; multivariate hazard ratio, 2.87 [95% confidence interval, 1.59-4.76]; P=0.0010) and overall survival (P=0.0027) that was independent of known prognostic factors and HER2 status. CONCLUSION: ASC identifies a rare aggressive HER2-negative subgroup of esophageal/gastroesophageal junction adenocarcinoma.
Assuntos
Adenocarcinoma/patologia , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Idoso , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/mortalidade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Junção Esofagogástrica/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
PURPOSE: Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well characterized. EXPERIMENTAL DESIGN: To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and nongestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including five gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (two to three different components each) and six pure choriocarcinomas, for somatic mutations, single-nucleotide polymorphisms, and PD-L1 expression. RESULTS: In mixed tumors, gynecologic-type carcinoma components demonstrated lineage-characteristic and lineage-specific alterations, with choriocarcinomatous components sharing some of these as well as demonstrating novel alterations, supporting a clonal relationship with divergent differentiation of the choriocarcinoma from the somatic carcinoma. TP53 mutation only occurred in nongestational tumors. Diffuse PD-L1 expression was characteristic of choriocarcinoma in both pure and mixed tumors but not seen in the gynecologic-type carcinoma components. CONCLUSIONS: Given that the somatic carcinomatous and choriocarcinomatous components of mixed tumors have distinct genetic alterations and biomarker expression, separate analysis of these components is required to guide targeted therapy. High PD-L1 expression suggests a role for checkpoint inhibitor-based immunotherapy in tumors with a choriocarcinoma component. The underlying mechanisms by which cancer stem cells reprogram and initiate trophoblastic retrodifferentiation in some somatic tumors warrant further investigation.
Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Linhagem da Célula , Coriocarcinoma/patologia , Neoplasias dos Genitais Femininos/patologia , Mutação , Neoplasias Uterinas/patologia , Adulto , Idoso , Diferenciação Celular , Coriocarcinoma/genética , Coriocarcinoma/metabolismo , Feminino , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/metabolismo , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismoRESUMO
A 3-day-old, 2.2-kg former 34-week premature infant with imperforate anus required loop ileostomy surgery. At delivery, the child had respiratory distress. Endotracheal intubation was "confirmed" by detection of exhaled carbon dioxide with a Pedi-Cap (Covidien, Dublin, Ireland) and subsequent chest x-ray. On arrival to the operating room, the pulse oximeter reading was 100% despite a large leak around the endotracheal tube and high-airway pressures. Packing the throat reduced the leak and increased the tidal volume. Intraoperative bronchospasm occurred during the surgery. On postoperative day 1, fiberoptic examination by an otolaryngologist revealed esophageal intubation and the absence of laryngeal opening. Subsequent computed tomography scan revealed Floyd type II tracheal agenesis. To our knowledge, this is the only case of tracheal agenesis diagnosed after a non-airway related procedure. We discussed how the diagnosis was missed.
Assuntos
Constrição Patológica/terapia , Esôfago , Intubação Intratraqueal/métodos , Traqueia/anormalidades , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/fisiopatologia , Erros de Diagnóstico , Evolução Fatal , Tecnologia de Fibra Óptica , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem , Traqueia/fisiopatologia , Resultado do TratamentoRESUMO
In our institution, the vast majority of patients presenting for noncardiac surgery (NCS) while supported by a left ventricular assist device (LVAD) are now cared for by noncardiac-trained anesthesiologists as the result of a decade of educational intervention to effect this transition. This represents a significant departure from the published experiences of other institutions. With institutional review board approval, we queried the database of our anesthesia record keeping system (CompuRecord) to determine various aspects of the perioperative management of these patients from July 1, 2003, through June 30, 2013, during which time 271 NCS procedures were performed on adult patients supported by LVADs. Over the entire study period (2003-2013), anesthetic care was provided by a cardiac anesthesiologist 47% of the time and by a noncardiac anesthesiologist 53% of the time. However, by the time period 2012-2013, 88% of the NCS procedures were staffed by a noncardiac anesthesiologist. Despite the prevalence of continuous flow devices in this series, the use of invasive blood pressure monitoring decreased dramatically by the later years of the study. Vasoactive and inotropic medications were rarely required intraoperatively. No intraoperative cardiac arrests, thromboembolic complications, or device malfunctions occurred. Our conclusion is that NCS procedures on LVAD-supported patients can be safely managed by educated noncardiac anesthesiologists.
Assuntos
Coração Auxiliar , Anestesia , Transfusão de Sangue , Feminino , Coração Auxiliar/efeitos adversos , Coração Auxiliar/tendências , Humanos , Masculino , Monitorização FisiológicaRESUMO
OBJECTIVES: Spindle cell lipomas (SCLs) are benign lipomatous neoplasms that classically arise in the posterior neck, upper back, and shoulders of older male patients. We sought to characterize the occurrence of this entity at nonclassic sites. METHODS: All cases of SCL arising at atypical sites were retrieved from our archives. RESULTS: Of 439 total cases of SCL, 57 arose at atypical locations in 32 men and 25 women (age range, 27-79 years). The tumor sites included leg (n = 23), buttock/perineum/inguinal (n = 10), forearm (n = 9), finger (n = 9), foot (n = 2), toe (n = 2), hand (n = 1), and flank (n = 1). CD34 was positive staining in all cases tested (52/52), while desmin was negative in most tumors (48/50). Thirty-eight of 38 cases tested exhibited loss of Rb expression. No cases showed CPM/MDM2 amplification (0/48). No local recurrences have been reported (n = 39). CONCLUSIONS: SCLs may arise in the trunk, lower extremities, and distal upper extremities. While most SCLs arising in classic sites occur in male patients, there is a relatively equal sex distribution in tumors at atypical sites. Pathologists should be aware that SCLs arise at atypical locations to avoid misclassification as other lipomatous neoplasms, including atypical lipomatous tumor.
Assuntos
Nádegas/patologia , Pé/patologia , Antebraço/patologia , Perna (Membro)/patologia , Lipoma/patologia , Neoplasias de Tecidos Moles/patologia , Tronco/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Lipoma/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecidos Moles/metabolismoRESUMO
Background. Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy. Results. We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism. Conclusions. Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.
RESUMO
Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study.
Assuntos
Biomarcadores Tumorais/genética , Fosfatases de Especificidade Dupla/genética , Rearranjo Gênico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Receptores Proteína Tirosina Quinases/genética , Adolescente , Adulto , Idoso , Quinase do Linfoma Anaplásico , Biópsia , Criança , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Anaplásico de Células Grandes/enzimologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Adulto JovemRESUMO
PURPOSE: There is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. We determined the frequency and prognostic impact of heterogeneous HER2 gene amplification and polysomy 17 in patients with esophageal adenocarcinoma (EAC). PATIENTS AND METHODS: HER2 amplification (by fluorescence in situ hybridization) was examined in surgical EAC specimens (n = 675). HER2 heterogeneity was defined according to consensus guidelines as gene amplification (HER2/CEP17 ratio ≥ 2.0) in more than 5% but less than 50% of cancer cells. No patient received neoadjuvant or HER2-targeted therapy. Cox models were used to assess disease-specific survival (DSS) and overall survival (OS). RESULTS: Overall, 117 EACs (17%) demonstrated HER2 amplification, of which 20 (17%) showed HER2 heterogeneity. All HER2-heterogeneous tumors were amplified. Among HER2-amplified tumors, heterogeneous tumors had significantly higher frequency of poor histologic grade and polysomy 17. In multivariable models that included number of metastatic lymph nodes, grade, tumor stage, and polysomy 17, only HER2 heterogeneity and node number were prognostic among HER2-amplified tumors, with heterogeneity showing worse DSS (hazard ratio, 2.04; 95% CI, 1.09 to 3.79; P = .025) and OS (P = .026). Among HER2-nonamplified EACs, polysomy 17 was independently associated with worse DSS (P = .012) and OS (P = .023). CONCLUSION: Among HER2-amplified EACs, 17% show HER2 heterogeneity, which independently predicts for worse cancer-specific death. Among HER2-nonamplified EACs, polysomy 17 is independently associated with worse survival. These novel findings demonstrate aggressive subgroups in HER2-amplified and -nonamplified EACs that have important implications for HER2 analysis and determination of benefit from HER2-targeted therapy.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Aneuploidia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Amplificação de Genes , Genes erbB-2 , Adenocarcinoma/cirurgia , Adulto , Idoso , Aberrações Cromossômicas , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Proteínas Associadas aos Microtúbulos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fosfoproteínas/genética , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
PURPOSE: We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression and gene amplification in patients with curatively resected esophageal adenocarcinoma (EAC). EXPERIMENTAL DESIGN: HER2 expression was analyzed by immunohistochemistry (IHC) in surgical EAC specimens (n = 713). Gene amplification was examined by FISH in a large subset (n = 344). Most tumors were T3-4 (66%) or node positive (72%); 95% were located in the esophagus or gastroesophageal junction. No patient received neoadjuvant therapy. Cox models were used. RESULTS: Overall, 17% of EACs were HER2 positive (i.e., IHC3(+) or IHC2(+) with amplification), with strong agreement between HER2 amplification (HER2/CEP17 ratio ≥2) and expression (κ = 0.83). HER2 positivity was significantly associated with lower tumor grade, less invasiveness, fewer malignant nodes, and the presence of adjacent Barrett's esophagus (BE). EACs with BE had higher odds of HER2 positivity than EACs without BE, independent of pathologic features [OR = 1.8 (95% CI: 1.1-2.8), P = 0.014]. Among all cases, HER2 positivity was significantly associated with disease-specific survival (DSS) in a manner that differed by the presence or absence of BE (P(interaction) = 0.0047). In EACs with BE, HER2 positivity was significantly associated with improved DSS [HR = 0.54 (95% CI: 0.35-0.84), P = 0.0065] and overall survival (P = 0.0022) independent of pathologic features, but was not prognostic among EACs without BE. CONCLUSIONS: HER2 positivity was shown in 17% of resected EACs and associated with reduced tumor aggressiveness. EACs with BE had nearly twice the odds of being HER2 positive and, within this subgroup, HER2 positivity was independently associated with improved survival.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias Esofágicas/metabolismo , Amplificação de Genes , Lesões Pré-Cancerosas/metabolismo , Receptor ErbB-2/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Esôfago de Barrett/genética , Esôfago de Barrett/metabolismo , Esôfago de Barrett/mortalidade , Esôfago de Barrett/patologia , Estudos de Coortes , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Dosagem de Genes , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/patologia , Prognóstico , Receptor ErbB-2/genética , Fatores de RiscoRESUMO
PURPOSE: Evaluate IVF-ET outcome data for a unique culture and cryopreservation strategy. METHODS: Retrospective study of 92 patients. Embryos for day-3 transfer were selected at pronuclear-stage; all extra zygotes were cryopreserved at pronuclear-stage. RESULTS: Delivery rates for Anonymous Oocyte Donation (Group I), patients <35 years (Group II), and 35-38 years (Group III) were 52.9%, 61.5%, and 51.7% for fresh and 38.5%, 33.3%, and 40.0% for frozen transfer. Deliveries per retrieval were 82.3%, 71.8%, and 58.6%. Only 0.88, 0.80, and 0.61 more zygotes were cultured than what were used for fresh transfer. Singleton, twin, and triplet rates were 64.6%, 31.2%, and 4.2% for fresh and 69.2%, 30.8%, and 0% for frozen. CONCLUSIONS: Selection of day-3 transfer embryos at the pronuclear-stage and cryopreservation of extra zygotes results in high delivery rates in fresh and frozen cycles. This approach optimizes deliveries per retrieval and provides many patients with more than one pregnancy per retrieval.