Significant Predictor Of Disease-free Survival Research Articles

Abstract A2: Receptor status in breast cancer and reproductive history: Is there any relation?

Abstract Objective: Molecular profiling studies using immunohistochemistry have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER-2) expression. These molecular subtypes and their combinations taken together with reproductive history of woman may help prognostication of breast cancer cases. We report a series of 102 cases of breast cancer treated in our institution over last five years (2004-08). Methods: Paraffin-embedded primary breast cancers from 102 patients with invasive and ductal carcinoma were studied immunohistochemically. Markers along with reproductive history were analysed. Result: 78 ductal 12 lobular cases were found. 43 cases were postmenopausal. Hormone receptor positive cases were 63 (61.7%), ER+ 34 (33.3%), and PR+ 29 (28.4%). HER-2/neu + cases were 34 (33.3%). There were 11 cases of triple negative (basal-like) breast cancer. Significant inverse correlation was found between HER-2/neu and hormone receptor. Early age at menarche was only found to be associated with risk of HER-2neu+, whereas breastfeeding had protective effect. Both late ages at menopause, hormone therapy was associated with poor prognosis. Higher age at first child birth was significantly associated with poorer outcome and no difference in risks with parity was noticed. HER-2/neu was not associated with response rate but their prognosis was worse. Triple negative had 3 survivors at three years. Significant associations were observed between HER-2/neu and increasing number of involved and metastases (p = 0.01). Analysis demonstrated that HER-2/neu overexpression (p = 0.02) and age (p = 0.01) were independent predictors for disease-free survival (DFS). Conclusion: Hormone receptor positive cases are associated with better prognosis than HER-2/neu positive cases. For node positive patients, HER-2/neu overexpression was a significant predictor of DFS. Reproductive history had significant bearing in prognosis and receptor expressing subsets of breast cancer which may be clear by further study. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A2.

Secondary cytoreductive surgery in the management of platinum‐sensitive recurrent epithelial ovarian cancer

To assess the surgical and survival outcomes after secondary cytoreductive surgery (SCRS) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) and to identify patients who would most benefit from SCRS. Inclusion criteria consisted of (1) recurrent EOC; (2) disease-free interval (DFI) >or=6 months after primary therapy; and (3) SCRS with therapeutic intent followed by adjuvant chemotherapy. Sixty-seven patients met the inclusion criteria in the interval 1992-2008. Median DFI was 20 months (range: 6-109 months). Median time in surgery was 240 min (range: 60-680 min), and median estimated blood loss was 100 ml (range: 50-3,000 ml). There was no significant perioperative complication requiring reoperation. Complete resection of all visible tumor tissue was achieved in 37 patients (55.2%), with residual tumors (RT) <or=1 cm remaining in four patients (6%). After a mean follow-up of 41 months (range: 6-145 months), the 2- and 5-year disease-free survival (DFS) rates were 32% and 10%, respectively, and the 2- and 5-year overall survival (OS) rates were 58% and 26%, respectively. In multivariable analysis, DFI >24 months and RT <or=1 cm were significant predictors of DFS and OS. SCRS is safe and effective, with a low rate of complications. Patients who benefited most from this surgery were those with a DFI >24 months and patients who achieved optimal cytoreduction.

Characteristics of Invasive Micropapillary Carcinoma of the Breast: In Comparison with Invasive Ductal Carcinoma

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast is a rare and associated with high incidence of lymph node metastasis and poor outcome. The aims of this study were to provide a comprehensive analysis of clinicopathologic and immunohistochemical characteristics of IMPC and to elucidate the differences between IMPC and invasive ductal carcinoma (IDC). Methods: Sixty-one patients of IMPC were identified by retrospective review of database from January 2004 to December 2008. 221 patients were randomly selected among the IDC patients who received operation during the same period. Two groups were compared with uni- and multivariate analysis. Results: We observed significant differences in mean number of metastatic lymph nodes (6.1 vs. 1.9, p= 0.001), positivity of lymph node (70.5% vs. 45.2%, p<0.001), and presence of lymphatic vessel invasion (75.4% vs. 34.8%, p <0.001) between IMPC and IDC patients. Although it has been known that triple negative breast cancer (TNBC) have lymphotropic tendency in their early T stage, 11.8% (26/221) of IDC and 3.3% (2/61) of IMPC patients were TNBC in this study (p=0.050). In multivariate analysis, IMPC histology showed no correlation with disease-free survival (DFS) and the lymphatic vessel invasion was a significant predictor of DFS. Conclusion: The results of this study confirm that IMPC is unique subtype of breast cancer that is commonly accompanied by axillary lymph node metastasis and shows poor outcome, although it rarely presents the pattern of TNBC. Lymphatic vessel invasion rather than histology of IMPC seems to be more closely related to DFS.

14-3-3 Sigma And p53 Expression in Gastric Cancer and Its Clinical Applications

14-3-3 sigma (σ) induces G2 arrest enabling the repair of damaged DNA. The function of 14-3-3 σ is frequently lost in tumor cells, indicating a potential tumor suppressor function. The purpose of this study was to evaluate the prognostic value of 14-3-3 σ expression in human gastric cancer. 14-3-3 σ expression was analyzed by immunohistochemistry in 157 tumor samples of patients, who underwent resection for gastric cancer. Since 14-3-3 σ is involved in the p53 network, p53 expression was detected in parallel and correlated with 14-3-3 σ. 14-3-3 σ was found to be overexpressed in 75 (47.8%) of 157 cases, the overexpression rate of p53 protein was 27.4%. 14-3-3 σ overexpression was statistically significantly associated with pT-stage (p=0.041) pN-stage (p=0.015) and UICC-stage (p=0.019) and showed a borderline significance with Lauren classification (p=0.057). Univariate survival calculations revealed a coexistent 14-3-3 σ and p53 overexpression as a significant predictor of disease-free survival. Multivariate analysis did not unfold 14-3-3 as an independent prognostic factor for disease-free survival and overall survival. Concomitant 14-3-3 σ and p53 overexpression in tumor cells of patients with gastric cancer identifies a population of patients with relatively unfavorable prognosis.

14-3-3 sigma and p53 expression in gastric cancer and its clinical applications.

14-3-3 sigma (σ) induces G2 arrest enabling the repair of damaged DNA. The function of 14-3-3 σ is frequently lost in tumor cells, indicating a potential tumor suppressor function. The purpose of this study was to evaluate the prognostic value of 14-3-3 σ expression in human gastric cancer. 14-3-3 σ expression was analyzed by immunohistochemistry in 157 tumor samples of patients, who underwent resection for gastric cancer. Since 14-3-3 σ is involved in the p53 network, p53 expression was detected in parallel and correlated with 14-3-3 σ. 14-3-3 σ was found to be overexpressed in 75 (47.8%) of 157 cases, the overexpression rate of p53 protein was 27.4%. 14-3-3 σ overexpression was statistically significantly associated with pT-stage (p=0.041) pN-stage (p=0.015) and UICC-stage (p=0.019) and showed a borderline significance with Lauren classification (p=0.057). Univariate survival calculations revealed a coexistent 14-3-3 σ and p53 overexpression as a significant predictor of disease-free survival. Multivariate analysis did not unfold 14-3-3 as an independent prognostic factor for disease-free survival and overall survival. Concomitant 14-3-3 σ and p53 overexpression in tumor cells of patients with gastric cancer identifies a population of patients with relatively unfavorable prognosis.

Dynamic Contrast-Enhanced MRI as a Predictor of Patient Outcome with Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Abstract Background: Early kinetic changes in DCE-MRI are predictive of clinical and pathologic response to neoadjuvant chemotherapy (NAC) in primary breast cancer (BC). Baseline vascular parameters and changes in these parameters with NAC have not been previously correlated with disease-free survival (DFS) and overall survival (OS) in BC.Methods: 73 patients (median age 45, range 26-70) with locally advanced BC due to undergo 4-6 cycles of anthracycline and/or taxotere NAC were imaged with DCE-MRI before and after 2 cycles as part of 2 prospective studies. Quantitative and semi-quantitative kinetic parameters such as Ktrans (inflow transfer constant) and IAUGC60 (initial area under the gadolinium-time curve) were derived from whole tumour regions of interest. Values for both baseline and changes in kinetic parameters as well as known prognostic indicators including age, grade, tumour size, nodal, hormonal and HER2 receptor status, and pathologic complete response were then correlated with DFS and OS using Kaplan-Meier analysis (log-rank test) and the Cox proportional hazards model. Median values for Ktrans and IAUGC60 were used to dichotomise data for survival analysis.Results: DCE-MRIs were performed in 62 patients before treatment (baseline group) and in 56 patients after 2 cycles of NAC. 3 were found to have metastatic disease after enrolment, 8 were not able to undergo both MRIs, 4 did not undergo their second MRI and in 2, the second scan was performed after 3 cycles of NAC. The median follow-up time for DFS was 33.7 months (range 0.3-75.6) and for OS 44.4 months (range 7.6-84.7). There were 21 distant recurrences in the baseline group (3 also had additional local recurrence) and 19 distant recurrences amongst those who were imaged pre and post treatment (2 also had local recurrence). There were 14 deaths in total (13 from BC, 1 from an unknown cause). Baseline DCE-MRI vascular parameters were not significantly associated with DFS or OS.Univariate analysis (n=56) using Cox regression showed age and ER positivity to be significant predictors of DFS &amp; a trend towards a longer DFS with greater reductions in Ktrans (HR 1.94, 95%CI 0.73-5.18; p=0.186) and in IAUGC60 (HR 1.98, 95%CI 0.74-5.28; p=0.172). Multivariate analysis for DFS demonstrated that changes in Ktrans (HR 2.18, 95%CI 0.79-6.05; p=0.133) and IAUGC60 (HR 2.11, 95%CI 0.78-5.74; p=0.142) remain potential prognostic indicators although results did not reach statistical significance. Both age and ER positivity were independent prognostic variables. Changes in DCE-MRI vascular parameters did not predict for OS.Conclusions: These results suggest that changes in DCE-MRI vascular parameters with reductions in Ktrans and IAUGC60, are associated with lower recurrence rates and could be potential prognostic biomarkers for DFS. A larger cohort is currently being studied to explore this further. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1092.

Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation

We report on a retrospective analysis examining the influence of pre-transplant serum ferritin on transplant outcomes of 99 MDS patients receiving reduced intensity conditioning (RIC) HSCT. The median pre-transplant ferritin value was 1992 ng/ml (range: 6–9580 ng/ml). No patients received iron chelation therapy preceding transplantation. On univariate analysis, there was a strong correlation between a higher pre-transplant serum ferritin (>1500 ng/ml) and a significantly inferior 3-year OS (64.6 ± 7.5% vs 39.6 ± 7.3%, p = 0.01). However, pre-transplant serum ferritin did not influence 3-year TRM (20.2 ± 7% vs 27.4 ± 7%, p = 0.24). There was no difference in infection-related mortality, and incidence of acute or chronic GvHD between cohorts. On multivariate analysis, a raised serum ferritin (HR: 2.00, 95% CI: 0.97–3.57, p = 0.03), and the presence of >5% bone marrow blasts at time of transplantation (HR: 2.14, 95% CI: 0.84–4.58, p = 0.06) were independent predictors of an inferior overall survival. However, pre-transplant serum ferritin was not a significant predictor of disease-free survival, relapse or TRM. When compared with myeloablative regimens, RIC regimens may attenuate the impact of iron overload related end-organ toxicity. Prospective studies incorporating alternative biomarkers of iron metabolism alongside serum ferritin levels are needed to improve our understanding of the significance of iron overload in MDS patients undergoing allogeneic transplantation.

Impact of Micrometastases in the Sentinel Node of Patients With Invasive Breast Cancer

Lymph node metastases are the most significant prognostic indicator for patients with breast cancer. Sentinel node biopsy (SNB) has led to an increase in the detection of micrometastases in the sentinel node (SN). This prospective study was designed to determine the survival impact of micrometastases in SNs of patients with invasive breast cancer. This study is based on the new sixth edition of the American Joint Committee on Cancer (AJCC) staging criteria. Between January 1, 1992 and April 30, 1999, 790 patients entered this prospective study at the John Wayne Cancer Institute. The SN was examined first by hematoxylin and eosin (HE), and if the SN was negative with HE, then immunohistochemical staining was performed. The patients were then divided into four groups based on AJCC nodal staging: pN0(i-), no evidence of tumor (n = 486); pN0(i+), tumor deposit < or = 0.2 mm (n = 84); pN1mi, tumor deposit more than 0.2 mm but < or = 2 mm (n = 54), and pN1, tumor deposit more than 2 mm (n = 166). Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The log-rank test was used to determine differences in DFS and OS of patients from different groups. At a median follow-up of 72.5 months, the size of SN metastases was a significant predictor of DFS and OS. Patients with micrometastatic tumor deposits, pN0(i+) or pN1mi, do not seem to have a worse 8-year DFS or OS compared with SN-negative patients. As expected, there was a significant decrease in 8-year DFS and OS in patients with pN1 disease in the SN.

Clinical and histopathological risk factors to predict sentinel lymph node positivity, disease-free and overall survival in clinical stages I–II AJCC skin melanoma: Outcome analysis from a single-institution prospectively collected database

Background To investigate if the tumour infiltrating lymphocytes (TILs) are able to predict the sentinel lymph node (SLN) positivity, the disease-free survival (DFS) and overall survival (OS) in clinical stages I-II AJCC primary cutaneous melanoma (PCM). Methods The study included consecutive patients with PCM, all diagnosed, treated and followed up prospectively. Logistic regression was used to investigate the association between DFS, OS, SLN positivity and Breslow thickness, Clark level, TIL, ulceration, lesion site, gender, regression and age. Results From November 1998 to October 2008, 1251 consecutive patients with PCM were evaluated. Median age was 51 (range 15–96) with 32.2% ( N = 393) of them older than 60; 44.8% of them were males. Of the whole series, a total of 404 patients with primary vertical growth phase (VGP) melanoma and no clinical evidence of metastatic disease underwent SLN biopsy. Of these, 74 (18.8%) had a positive SLN. In a multivariate analysis, primary melanoma on the extremities versus that on the axial locations (truncal and head/neck) (OR 0.49, 95% CI 0.25–0.98, p 0.04) and TILs (TILs versus no TILs) (OR 0.47, 95%CI 0.25–0.90, p 0.02) were predictive for lower probability of SLN involvement, while thickness (>4 mm versus 0–1 mm) (OR 24, 19, 95% CI 4.91–119.13, p < .001) was predictive for higher risk of SLN positivity. A multivariate stepwise analysis confirmed these results. The histological status of the SLN was the most significant predictor of DFS and OS. Patients with a negative SLN had a 5-year DFS of 75.9%, compared with 35.2% in patients with a positive SLN ( p < .0001) and a 5-year OS of 88.7% versus 42.9%, respectively ( p < .0001). Conclusions Our study demonstrates that the absence of TILs predicts SLN metastasis, in multivariate analysis the SLN positivity predicts DFS and OS.

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

Although adjuvant chemoradiation is used commonly in the United States for the treatment of resected pancreatic cancer, there is no consensus on the benefit of this therapy, because the results from randomized trials are conflicting. The authors of this report reviewed their experience in a consecutive, unselected series of patients who received adjuvant 5-fluorouracil (5-FU) and radiation therapy (RT) for resected pancreatic adenocarcinoma. Eighty-six patients with resected pancreatic adenocarcinoma who received adjuvant therapy from 1998 to 2005 were identified, and their medical records were reviewed. Ninety-three percent of patients were treated with external beam RT to > or =50.4 grays, and 91% of patients received concurrent 5-FU by continuous infusion. Forty-five percent of patients went on to receive adjuvant gemcitabine. The median follow-up was 31 months (range, 21-62 months) among the 20 patients who remained alive. Less than half of patients had positive (33%) or close (<1 mm; 15%) resection margins, 81% of tumors were classified as T3, and 66% of patients had involved lymph nodes. The median overall survival (OS) for all patients was 22 months. Negative lymph node status (P = .016) was a significant prognostic factor for improved OS, whereas treatment with gemcitabine trended toward improved OS (P = .080). The median disease-free survival (DFS) for all patients was 10 months: Treatment with gemcitabine (P = .044) and the receipt of any chemotherapy (P = .047) were significant predictors of DFS. Seventy-five patients (87%) had disease recurrence, and the majority recurred with peritoneal metastases (55%) or liver metastases (53%). Patients who had negative lymph nodes trended toward a lower rate of distant failure (P = .060). The median survival of the current cohort was greater than that of the chemoradiation arms of European Organization for Research and Treatment of Cancer trials and European Study Group for Pancreatic Cancer 1 trials and was comparable to the survival observed on the Gastrointestinal Tumor Study Group chemoradiation arm. Lymph node status and treatment with adjuvant chemotherapy were significant predictors of OS and DFS, respectively. Future survival improvements should be directed at reducing peritoneal and liver metastases. Further randomized trials will be required to define the role of adjuvant therapy for pancreatic adenocarcinoma.

Prognostic value and clinicopathological significance of p53 and PTEN in epithelial ovarian cancers

Objective The aim of the study was to evaluate the prognostic significance of p53 and PTEN in patients with epithelial ovarian cancer who were treated with taxane and platinum-based chemotherapy. Methods Retrospectively collected paraffin blocks from 151 epithelial ovarian cancer patients treated with debulking surgery followed by taxane and platinum chemotherapy were analyzed. Expression of p53 and PTEN was assessed by immunohistochemistry. The staining pattern was correlated with clinicopathological variables. Results Overexpression of p53 was found in 80 of the 151 cases (53.0%), and it was related to stage, histology and grade. Reduced expression of PTEN was found in 104 of the 151 cases (68.9%), and it was not related to any clinicopathological factors other than age. In survival analysis, stage ( p = 0.001), residual tumor ( p = 0.045), lymph node metastases ( p = 0.012), and PTEN expression ( p = 0.009) were significant predictors for disease-free survival (DFS). The median DFS of patients with reduced PTEN expression was 20 months (range, 3–71 months), whereas that of patients with normal PTEN expression was 53 months (range, 2–81 months). Conclusions Reduced PTEN expression is a poor prognostic factor for DFS in patients with epithelial ovarian cancer who were treated with debulking surgery and postoperative taxane and platinum chemotherapy.

Risk assessment of relapse in Swiss participants of BIG 1-98 with grade 2 early breast cancer by gene expression profiling using RNA from formalin-fixed, paraffin embedded (FFPE) tissue.

Abstract Abstract #1073 BIG 1-98 is a randomized controlled clinical trial for postmenopausal patients with early, estrogen and/or progesterone receptor (ER/PgR) positive breast cancer. It compares adjuvant therapy with 5 years of tamoxifen (T) or letrozole (L), two years of T followed by 3 years of L (T→L) or vice versa (L→T). L improved disease free survival (DFS) over T by 18% (hazard ratio 0.82, JCO 2007;25:486ff). Switzerland contributed 598/8010 patients. The patient and tumor characteristics of Swiss patients was similar to the entire BIG 1-98 population. The purpose of this study was to test a prognostic score in RNA derived from FFPE tissues.&amp;#x2028; Scores representing ER and progesterone receptor (PgR) function, proliferation (PRO14, AURKA/STK15, BIRC5/SURV, CCNB1, CCNB2, CCNE2, CDC2, ENPF, KIF20A, MKI67, MYBL2, ORC6L, PRC1, SPAG5, TOP2A), and HER-2 were built from multiple genes for each score. Genes were selected according to an analysis of publicly available cDNA array databases. In a prior set of 82 pairs of breast cancer samples the Pearson correlation coefficients of the scores between fresh frozen and FFPE tissues were at least 0.94. Cut-offs for ER and HER-2 scores were defined as the antimodes of fitted bimodal Gaussian distributions; the ER and HER-2 scores closely agreed with immunohistochemical (IHC) data (kappa(ER)=0.868, kappa(HER-2)=0.836).&amp;#x2028; FFPE tissues were available from 437 Swiss BIG 1-98 patients. RNA of sufficient quantity and quality was extracted from 388 blocks (89%). Forty-seven genes were quantified by QRTPCR on TaqMan Low Density Arrays (TLDAs) as reported previously (Proc AACR 2008, Abstract 974).&amp;#x2028; The PRO14 score was positively correlated with the histological grade. PRO14 scores greater than the median and PGR scores lower than the median were associated with shorter DFS. In patients with grade 2 tumors, PRO14 scores were significant predictors of DFS in univariate Cox regression analyses. Multivariate analyses will be presented. Our findings are in agreement with an analysis of fresh frozen tissues of Belgian participants in BIG 1-98 (European Breast Cancer Conference 2008, Abstract 481).We show that RNA can be extracted from FFPE in sufficient quantity and quality to be used in QRTPCR using TLDAs. This opens the possibility of using FFPE tumor banks from controlled clinical trials for the investigation of gene expression patterns. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1073.

The prognostic value of nuclear morphometric analysis in serous ovarian carcinoma

The objective of this study was to determine whether nuclear morphometric data can predict survival, disease progression, and chemotherapeutic response in ovarian serous carcinoma. Nuclear morphometric parameters were determined from archival hematoxylin and eosin sections of 132 serous tumors. Clinicopathologic and morphometric parameters were evaluated as to their individual and independent prognostic value and prediction of chemotherapy response. Nuclear parameters were found to strongly correlate with extent of disease residuum, tumor grade, and FIGO stage. Univariate analysis revealed stage, grade, preoperative CA125, presence of ascites, extent of disease residuum, standard deviation of nuclear area (SDNA), nuclear perimeter (NP), SDNP, nuclear length (NL), nuclear breadth (NB), orthoferet, and equivalent diameter (ED) to be significant predictors of overall survival (OS) and disease-free survival (DFS). Grade, stage, extent of disease residuum, presence of ascites, SDNA, NP, NL, NB, and orthoferet were found to be significant predictors of chemotherapy response. Multivariate analysis revealed extent of disease residuum (P≤ 0.01) and ED (P= 0.002) to be significant predictors for OS. FIGO stage (P≤ 0.01) and ED (P= 0.039) were significant predictors of DFS. NL (P= 0.041) and extent of residual disease (P= 0.003) were the strongest predictors of chemotherapy response with correct classification rates of 68.8% and 70.3%, respectively. In all stages, nuclear morphometry was easy to perform and highly reproducible. Independent prognostic significance was achieved for OS and DFS analysis. Results also suggest that nuclear morphometry can provide significant information to predict chemotherapy response in platinum-treated serous ovarian cancer.

Predictors of clinical outcome in triple negative breast cancer: An institutional review

22180 Background: Triple negative (−) breast cancer (BC) is defined as lack of expression of estrogen, pregesterone and Her2 neu, being considered a high risk group. We study the pathological characteristics and the clinical outcome of a cohort of 64 consecutive triple negative(−) BC patients (pts) diagnosed at our institution. Methods: between january 1999 and june 2007, 64 (stage I to III) triple(−) BC pts. were retrospectively analyzed. All the Pts. had their receptor status and staining for Her neu by a single pathologist at the Institute of Oncology “Ángel H.Roffo”, (UBA). Univariate and multivariate analysis for the risk factors associated with relapse, and the log rank test for disease free survival (DFS), and overall survival (OS) was performed. Results: The median age was 52 years (range, 28–84 years).The median follow up time was 32 months (range, 3.−106). Overall, relapse rate is 42% (n=27), and 56 Pts (87.5%) are alive. Median DFS was 23 months (range, 3–106 months). Stage at the time of presentation was: 14 (22%) stage I; 29 (47%) stage II; 21 (31%) stage III. Pre-menopausal status was 46.6%, and 41% were limph node positive. Median OS: Stage I, II, and III was 33 (3–106), 30 ( 6–87), and 20 months (6–53) respectively, (p=0.0186). Median DFS: stage I, II and III was 33 (3–106), 27 (6–87), and 16 months (5–38) respectively, (p=0.0011). Pathological parameters analyzed ( nuclear grade, histologic grade, mitotic index and vascular invasion) were not significant predictors for DFS and OS by multivariate analysis, however vasculo-lymphatic invasion showed significance for both clinical outcomes in the univariate analysis, (p value 0.04 and 0.02, respectively). Conclusions: Triple (−) BC has an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up. In this triple (−) population only stage of disease was the only independent prognostic factor for DFS and OS. Between the pathological features analyzed only vasculo-lymphatic invasion seems to have prognostic significance. No significant financial relationships to disclose.

REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis

By expression profiling of early staged colon carcinomas, we found regenerating islet-derived 1 alpha (REG1A) to be upregulated in patients with an unfavorable clinical outcome. For validation, REG1A expression was quantified in another colorectal cancer (CRC) patient cohort by Taqman PCR. Aside from tumor and normal tissue from 63 nonpretreated CRC patients, 31 mucosa biopsies from healthy individuals as well as 22 adenomas were included in the investigation. REG1A was significantly upregulated in tumor specimens (p < 0.001) and adenoma (p < 0.01) as compared to normal colorectal tissue. REG1A expression in normal peritumoral tissue in turn proved to be significantly elevated compared to mucosa from healthy individuals (p < 0.01). Determination of REG1A expression might be useful for early tumor diagnosis with a sensitivity of 90.6%, and a specificity of 77.9%. REG1A expression was significantly increased in tumors with peritoneal carcinomatosis (p < 0.01). Moreover, REG1A turned out to be a significant predictor of disease-free survival (p < 0.05). In conclusion, we present evidence that REG1A is a molecular marker of prognostic value and is associated with peritoneal carcinomatosis in CRC. REG1A turned out to be already significantly raised in peritumoral normal tissue compared to mucosa from healthy individuals, suggesting a molecular field effect of secreted REG1A.

Visceral Obesity May Affect Oncologic Outcome in Patients with Colorectal Cancer

Obesity is closely related to the development of colorectal cancer as well as other metabolic complications. We investigated the prognostic significance of visceral obesity and body mass index (BMI) in 161 resectable colorectal cancer patients. Ratios of visceral fat area (VFA) to subcutaneous fat area (SFA) were measured from the digital images of patients' computed tomography taken before the surgery, and patients were divided into those with high and those with low VFA/SFA ratio according to the degree of proportional visceral adiposity, and into an overweight and a normal-weight group according to their preoperative BMI. The overweight group showed a borderline decrease in cumulative disease-free survival compared to the normal-weight group (P = 0.064). Patients with high VFA/SFA ratio (more than 50 percentiles) had significantly lower cumulative disease-free survival rate compared to patients with low VFA/SFA ratio (P = 0.008). BMI and visceral adiposity showed no influence on overall survival of patients. Increased visceral adiposity was a significant predictor of disease-free survival in patients with resectable colorectal cancer. The prognostic significance of visceral adiposity should further be determined in a larger set of patients.

The Prognostic and Predictive Value of Syntactic Structure Analysis in Serous Carcinoma of the Ovary

The objective of this study was to determine whether syntactic structure analysis (SSA) can predict survival outcome and chemotherapeutic response in ovarian carcinoma. Syntactic structure analysis parameters, blindly determined in archived hematoxylin and eosin sections of 132, International Federation of Gynecology and Obstetrics (FIGO) stage I to IV serous ovarian tumors, and clinicopathologic parameters were evaluated as to their univariate and multivariate prognostic value and ability to predict chemotherapy response as measured by changes in CA125 levels. Univariate analysis revealed FIGO stage, tumor grade, preoperative CA125, presence of ascites, extent of disease residuum, and the SSA parameters minimum spanning tree (min MST), maximum MST (max MST), percent connectivity to 1, and 2 nearest neighbors to be significant predictors of overall survival and disease-free survival. Tumor grade, FIGO stage, extent of disease residuum, presence of ascites, and percent connectivity to 2 nearest neighbors were found to be significant predictors of chemotherapy response. Multivariate analysis revealed extent of disease residuum to be a significant predictor for overall survival (P <or= 0.01) and prediction of chemotherapy response (P = 0.05). International Federation of Gynecology and Obstetrics stage was a significant predictor for disease-free survival (P <or= 0.01). Syntactic structure analysis parameters did not retain independent significance. Syntactic structure analysis features can predict survival outcome and chemotherapy response in ovarian carcinoma but, with multivariate analysis, are overshadowed by FIGO stage and residual disease.

Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

To investigate the changing pattern of beta-catenin expression and its prognostic value in advanced colorectal cancer (CRC). Archival tumor samples were analyzed for beta-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. Membranous beta-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted disease-specific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). Nuclear beta-catenin expression provides additional information in predicting patient outcome in advanced CRC.

Estrogen Receptor Subtypes in Ovarian Cancer

To study the distribution of estrogen receptor (ER) subtypes in ovarian tumors and to correlate the levels of expression with clinical factors. Estrogen receptor-alpha (ERalpha) and beta-mRNA expressions in 58 normal, 25 borderline, and 161 malignant ovarian tissue samples were determined by quantitative real-time polymerase chain reaction. The expression levels were correlated with clinical data, including the histologic subtypes, the stage of the disease, and the disease-free and overall survival, with a median follow-up of 80 months. Estrogen receptor-beta (ERbeta) expression, but not ERalpha, was significantly higher in normal tissues compared with malignant tissues (P<.001). Estrogen receptor-beta expression was also significantly higher in stage I disease compared with stage II-IV disease (P<.001). A higher ERbeta expression was found to be significantly associated with a longer disease-free survival (P=.007) as well as overall survival (P=.011). Estrogen receptor-beta expression remained a significant predictor for disease-free survival and overall survival in multivariable analysis that took into account other factors that were shown to be associated with survival in univariate analyses, including stage of disease, type of tumor (borderline or malignant), and optimal debulking. Loss of ERbeta expression in ovarian tumors may be a feature of malignant transformation. Determining ER subtypes expression may improve response to hormonal therapy by tailoring the use of selective estrogen receptor modulators with different ER affinity in selected women. As a prognostic indicator, ERbeta levels may be useful in deciding the need for and choice of adjuvant treatment in women with early ovarian cancers. II.

P53 and bcl-2 assessment in serous ovarian carcinoma

The study objective was to determine the prognostic value of assessment of staining of p53 and bcl-2 in a well-selected group of serous ovarian carcinomas. Immunohistochemical detection was used to identify both p53 and bcl-2 positive tumors. One hundred thirty-two tumors were analyzed for positivity of staining, grade of staining intensity, and for p53 alone, percent expression rates. These were analyzed alongside traditional clinicopathologic parameters for their ability to predict overall survival (OS), disease-free survival (DFS), and response to chemotherapy (CR). Univariate COX analysis revealed percent p53 expression (P = 0.012) and p53 grade (P = 0.01) to be significant predictors of DFS. Neither the p53 nor bcl-2 measurement parameters were found significant for OS or prediction of CR. On multivariate analysis, incorporating clinicopathologic parameters, p53 parameters did not retain independent significance for any outcome measure. As in primary reported studies, bcl-2 was not found to be of clear independent prognostic value in this group of ovarian tumors. If mutation of p53 and its consequent overexpression is an early event in ovarian tumorigenesis, then p53 assessment may prove useful prognostically in the assessment of either low-grade ovarian carcinomas, as a possible indicator for progression, or in early-stage ovarian tumors, as a marker of tumor aggression or likelihood of recurrence. p53 analysis of a larger group of stage I ovarian tumors would be desirable to further explain the potential association with DFS.