Purpose: To evaluate the usefulness and the pitfalls inherent to the assessment of the epidermal growth factor receptor (EGFR) gene copy number (GCN) by fluorescence in situ hybridization (FISH) for outcome prediction to cetuximab in metastatic colorectal cancer. The value of testing KRAS mutation status, in addition to EGFR GCN, was also explored. Experimental Design: FISH analysis of 87 metastatic colorectal cancer patients treated with cetuximab was done, recording individual GCN per cell and using different samples per tumor. Performances of published cutoff points and different summaries of EGFR GCN distribution were assessed for response prediction. Results: In our data set, two published cutoff points performed less well than in their training set, yielding positive predictive values and negative predictive values between 40.0% and 48.3% and between 81.0% and 86.5%, respectively. Among summaries of GCN distribution explored, mean and right-tailed distribution of GCN yielded the highest performances. A mean EGFR GCN z2.83 provided an area under the curve of 0.71. Important heterogeneity of repeated measures of mean EGFR GCN was observed within tumors (intraclass correlation, 0.61; within-class SD, 0.40), leading to potential misclassifications of FISH status in 7 of 18 (38.8%) patients if a cutoff point were used. In multivariable analysis, EGFR GCN testing provided significant information independent of the KRAS status to predict response (P = 0.016) and overall survival (P = 0.005). Conclusions: We confirm the association between increased EGFR GCN and outcome after cetuximab. However, because of reproducibility concerns, any decision making based on published cutoff points is not warranted.Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of a variety of agents, including small inhibitory molecules and monoclonal antibodies (mAb). Two such mAbs, panitumumab and cetuximab, are active in metastatic colorectal cancer, but only subgroups of patients respond to these agents (1 -3) and reliable markers predictive of treatment benefit still need to be defined.Variations of gene copy numbers (GCN), either in terms of gains or losses, reflect the many different routes taken by individual tumors to disrupt/escape mechanisms governing normal cellular behavior. These genomic aberrations have been successfully investigated by fluorescence in situ hybridization (FISH) in a number of malignancies. Importantly, three recently published series have reported on enhanced sensitivity to anti-EGFR mAbs in colorectal cancer patients harboring an increase of mean EGFR GCN by FISH (4 -6). In most solid tumors, including non -small-cell lung cancer and colorectal cancer, the best characterized mechanisms underlying increased EGFR GCN are gene amplification and chromosome 7 polysomy (4 -7). Generally, amplification is representative of high-level genomic gain and it is readily identifiable by FISH. Conversely, polysomy mirrors variable degrees of chromosomal ga...

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BACKGROUND: To investigate the value of neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), in endometrial cancer with transperitoneal spread (stage IV). METHODS: Patients with endometrial cancer with transperitoneal spread, as determined by laparoscopy ( ± pleural effusion), were treated with NACT. Efficacy was determined according to the Response Evaluation Criteria in Solid Tumors, residual tumour at IDS and histopathological assessment of tumour regression. RESULTS: A total of 30 patients (median age: 65 years; range:44 -81 years) received 3 -4 cycles of NACT (83% paclitaxel/carboplatin). Histopathological subtypes were as follows: serous (90%), clear cell (3%) and endometrioid (6%) carcinoma. Response according to RECIST was as follows: 2 (7%) complete remission, 20 (67%) partial remission, 6 (20%) stable disease and 2 (7%) progressive disease (PD). Patients with PD were not operated upon. A total of 24 patients (80%) had optimal cytoreduction (R p1 cm), of whom 22 (92%) were without residual tumour. Four patients were considered inoperable and were excluded from further analysis. The median progression-free survival and overall survival times were 13 and 23 months, respectively. Histopathological features of chemoresponse in both uterus and omentum were related to a better PFS (P ¼ 0.017, hazard ratio (HR) ¼ 0.785) and overall survival (P ¼ 0.014, HR ¼ 0.707). In particular, the absence of tumour infiltration and necrosis were associated with prognosis. CONCLUSION: The use of NACT resulted in a high rate (80%) of optimal IDS for the treatment of endometrial cancer with transperitoneal spread.

We report a case of polypoid bladder endometriosis in pregnancy. Diagnostic CASE REPORTA 29-year-old primigravida was referred at 19 weeks' gestational age with intermittent hematuria that had occurred since 8 weeks. Vaginal examination revealed a 2-cm-diameter retropubic nodule that was slightly tender on palpation. Microscopic urinalysis showed no malignancy. Ultrasonographically, a well-vascularized mass (30 × 23 × 25 mm) was visualized, which protruded into the vesicouterine pouch but did not interrupt the hyperechogenic layers of the bladder wall (Figure 1a). Color Doppler showed strong (score 4) internal blood flow (Figure 2a). Magnetic resonance imaging (MRI) confirmed the presence of a solid and polypoid mass, located at the junction of the urachal ligament and the bladder dome, extending into the wall of the bladder (Figure 3a). This mass showed intermediate to high signal intensity on T2-weighted imaging. The T1-weighted images showed no foci of intralesional hemorrhage. As a result of this location and the signal-intensity characteristics, a malignancy of the urachus was suspected, without evidence of metastatic disease. During cystoscopy, a polypoid mass was visualized in the anterior bladder wall that was covered by bladder mucosa. The typical red-brown lesions, which are hallmarks of endometriosis, were absent, and no biopsy was performed in view of the risk of major bleeding from this wellvascularized mass. After multidisciplinary discussion, an abdominal exploration and partial cystectomy were performed. The urachus was dissected and extracted en bloc with the tumoral lesion. No other abdominal tumors were found. Gross examination of the resected specimen showed a white, rather soft and irregular mass. Microscopically the lesion consisted of glandular structures lined with an endometrial type of epithelium with Arias-Stella phenomena. These glandular structures invaded the muscular bladder wall and were surrounded by a massively decidualized stroma. Focally, the lesion also protruded through the bladder mucosa with the formation of a polypoid structure in the lumen of the bladder. These observations led to the diagnosis of pseudotumoral (polypoid) endometriosis. Postoperative recovery was uneventful, with no adverse effect on the pregnancy. DISCUSSIONGestational decidual changes of endometrial tissue in endometriosis may manifest as polypoid nodules and mimic malignant transformation. Decidualization depends on the action of estrogen, progesterone and factors secreted by the implanting blastocyst during trophoblast invasion. These decidual changes can cause differential diagnostic problems, which have been well

In contrast to theoretical assumptions, the current study did not reveal evidence that the expression of ERCC1 and class III β-tubulin predicts response to cytotoxic treatment and patient outcome in endometrial cancer.

: On the basis of the absence of KIT expression or mutations, endometrial carcinoma is unlikely to respond to imatinib mesylate.

<div>Abstract<p><b>Purpose:</b> To evaluate the usefulness and the pitfalls inherent to the assessment of the epidermal growth factor receptor (<i>EGFR</i>) gene copy number (GCN) by fluorescence <i>in situ</i> hybridization (FISH) for outcome prediction to cetuximab in metastatic colorectal cancer. The value of testing <i>KRAS</i> mutation status, in addition to <i>EGFR</i> GCN, was also explored.</p><p><b>Experimental Design:</b> FISH analysis of 87 metastatic colorectal cancer patients treated with cetuximab was done, recording individual GCN per cell and using different samples per tumor. Performances of published cutoff points and different summaries of <i>EGFR</i> GCN distribution were assessed for response prediction.</p><p><b>Results:</b> In our data set, two published cutoff points performed less well than in their training set, yielding positive predictive values and negative predictive values between 40.0% and 48.3% and between 81.0% and 86.5%, respectively. Among summaries of GCN distribution explored, mean and right-tailed distribution of GCN yielded the highest performances. A mean <i>EGFR</i> GCN ≥2.83 provided an area under the curve of 0.71. Important heterogeneity of repeated measures of mean <i>EGFR</i> GCN was observed within tumors (intraclass correlation, 0.61; within-class SD, 0.40), leading to potential misclassifications of FISH status in 7 of 18 (38.8%) patients if a cutoff point were used. In multivariable analysis, <i>EGFR</i> GCN testing provided significant information independent of the <i>KRAS</i> status to predict response (<i>P</i> = 0.016) and overall survival (<i>P</i> = 0.005).</p><p><b>Conclusions:</b> We confirm the association between increased <i>EGFR</i> GCN and outcome after cetuximab. However, because of reproducibility concerns, any decision making based on published cutoff points is not warranted.</p></div>

Supplementary Tables S1-S4 from Clinical Usefulness of <i>EGFR</i> Gene Copy Number as a Predictive Marker in Colorectal Cancer Patients Treated with Cetuximab: A Fluorescent <i>In situ</i> Hybridization Study