High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin’s Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as ‘low expressing’ (< 20% of tumor cells) or ‘highly expressing’ (≥ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases;p= 0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases;p= 0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (~20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (~70% at 5 year). This correlation was statistically significant (log-rank test,p= 0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.

Download Full-text

NCOG-02. PROGNOSTIC VALIDATION OF THE EANO ESMO CLASSIFICATION OF LEPTOMENINGEAL METASTASIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.541 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii129-ii129

Author(s):

Emilie Le Rhun ◽

Patrick Devos ◽

Johannes Weller ◽

Katharina Seystahl ◽

Francesca Mo ◽

...

Keyword(s):

Tumor Cells ◽

Leptomeningeal Metastasis ◽

Rank Test ◽

Type I ◽

Type Ii ◽

Primary Tumors ◽

Kaplan Meier ◽

Negative Prognostic Factor ◽

Choice Of Treatment

Abstract BACKGROUND The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes for choice of treatment and outcome. PATIENTS AND METHODS We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. RESULTS Median age at LM diagnosis was 56.5 years (range 20-82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138). CONCLUSION The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

Download Full-text

Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa- associated lymphoid tissue localization

Blood ◽

10.1182/blood.v84.11.3785.bloodjournal84113785 ◽

1994 ◽

Vol 84 (11) ◽

pp. 3785-3791 ◽

Cited By ~ 80

Author(s):

PC de Bruin ◽

JA Kummer ◽

P van der Valk ◽

P van Heerde ◽

PM Kluin ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Cells ◽

Lymphoid Tissue ◽

Cytotoxic T Cells ◽

Granzyme B ◽

Clinical Behavior ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas ◽

Peripheral T Cell Lymphomas

T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa- associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T- cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T- cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.

Download Full-text

41. PROGNOSTIC VALIDATION OF THE EANO ESMO CLASSIFICATION OF LEPTOMENINGEAL METASTASIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.029 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii7-ii8

Author(s):

Emilie Le Rhun ◽

Patrick Devos ◽

Johannes Weller ◽

Katharina Seystahl ◽

Francesca Mo ◽

...

Keyword(s):

Tumor Cells ◽

Leptomeningeal Metastasis ◽

Rank Test ◽

Type I ◽

Type Ii ◽

Primary Tumors ◽

Log Rank Test ◽

Kaplan Meier ◽

Negative Prognostic Factor

Abstract BACKGROUND The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes. PATIENTS AND METHODS We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. RESULTS Median age at LM diagnosis was 56.5 years (range 20–82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells were observed in the CSF in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138). CONCLUSION The presence of tumor cells in the CSF appears to have a greater prognostic role than the neuroimaging presentation. EANO ESMO LM subtypes are highly prognostic and should be considered in the design of clinical trials.

Download Full-text

Diverse clinical outcome and predictors for clinical outcome in patients with HCC treated with TACE.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.442 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 442-442

Author(s):

Prarthna Bhardwaj ◽

Petra Prins ◽

Alexander Y. Kim ◽

Rheena Jha ◽

Hongkun Wang ◽

...

Keyword(s):

Clinical Outcome ◽

Progression Free Survival ◽

Rank Test ◽

T Stage ◽

Kaplan Meier ◽

Stage Disease ◽

T4 Stage ◽

Poorly Differentiated ◽

Well Differentiated ◽

Tace Treatment

442 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the second leading cause of cancer-related death, worldwide. This reflects the challenges facing HCC treatment. Methods: Patients (pts) with HCC receiving TACE treatment (n = 96) were examined retrospectively for clinical outcome and its possible predictors. The number of TACE treatments and the time elapsed between each treatment were assessed and correlated with overall survival (OS) using the log rank test of Kaplan Meier curves. T-stage, level of differentiation, vascular invasion, and Child Pugh score at the time of HCC diagnosis were compared among pts who received different numbers of TACE treatments (Kaplan-Meier survival analysis, ANOVA and student T test). Results: TACE treated pts had a median OS of 46 month (mo) and progression free survival of 12 mo (difference in time between the date of first progression and the date of diagnosis). Pts received 1-2 (n = 52), 3-4 (n = 28), or 5-6 (n = 16) TACE treatments. We found that pts who had only 1-2 TACE treatments had significantly shorter median OS (38 mo) than those who received 3-4 or 5-6 treatments (48 and 83 mo; p < 0.05). Of the 96 pts studied 22, 33, 37, and 3 pts had T1, T2- T3 and T4-stage HCC, respectively. Only 39 pt tumors underwent pathological analysis, and 13 were well-differentiated (WD), while 24 were moderately- or poorly- differentiated (MPD) (p > 0.05). Tumor T-stage and differentiation were correlated with the number of TACE treatments received. Thus, 30% of pts (n = 10) with T2-stage disease compared with 10% (n = 4) with T3-stage disease received 5-6 TACE treatments (p < 0.001). Similarly, 30% of WD cases (n = 4) compared with only 8% of MPD cases (n = 2) received 5-6 TACE treatments (p < 0.001). The duration between the second and third TACE treatments ( < 4 mo, 5-8 mo or > 8 mo) seemed to correlate with outcome (p < 0.05). Conclusions: Pt survival time following TACE treatment is diverse and correlates with the number of TACE treatments. Pts with T3-stage, or MPD HCC tended to receive fewer TACE treatments than those with T2-stage or WD HCC, and have worse outcomes. Other therapies should certainly be considered for pts with T3-stage and/or MPD tumors.

Download Full-text

Arginine methylation of EGFR in circulating tumor cells: A new biomarker for predicting resistance to anti-EGFR agents.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3590 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3590-3590

Author(s):

Krittiya Korphaisarn ◽

Chao-Kai Chou ◽

Weiya Xia ◽

Callisia Clarke ◽

Jennifer S Davis ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Arginine Methylation ◽

Rank Test ◽

Positive Staining ◽

Egfr Ligands ◽

Kaplan Meier

3590 Background: Arginine methylation of the epidermal growth factor receptor (meEGFR) increases binding affinity of EGF and other EGFR ligands, reduces the efficacy of anti-EGFR agents in vivo, and is reported to have a role in predicting response to anti-EGFR agents. This study aimed to investigate the predictive impact of meEGFR in metastatic colorectal cancer (mCRC) patients (pts) treated with anti-EGFR agents using blood-based testing. Methods: 15 mL of blood were collected from mCRC pts with documented disease progression following anti-EGFR treatment (Rx). Circulating tumor cells (CTCs) were isolated using antibody (ab)-independent micro-fluidic cassette-based technology (Parsortix system), which separates CTCs on the basis of size and deformability. CTCs were identified based on negative staining for CD45ab and positive staining for EpCAMab. meEGFR was identified based on positive staining for me-R198/200ab on CTCs. Associations between meEGFR-CTCs and total CTCs with progression free survival (PFS) were determined by Kaplan-Meier method and compared by the log-rank test. Results: A total of 47 mCRC pts were prospectively included in this study. CTCs were identified in 30 out of 47 cases (64%). Of those 30, meEGFR-CTCs were identified in 19 cases (63%). Mean total CTCs and meEGFR-CTCs counts were 3.6 (range 0-52) and 2.3 (range 0-30) cells per 7.5ml, respectively. There was no association between meEGFR-CTCs and clinic-pathological features (age, sex, tumor site & grade), line of anti-EGFR Rx, previous irinotecan used, or NRAS, BRAF, PIK3CA, and MSI status. However, in RASwt/BRAFwtmCRC pts, high levels of meEGFR ratio (defined as > 0.25 meEGFR-CTCs per total CTCs) was associated with significantly inferior PFS with anti-EGFR Rx (median PFS 5.4 mo vs. 8 mo, HR 3.4, 95% CI of 1.5-7.9, P = 0.004). By contrast, high levels of total CTCs ( > 3 cells/per 7.5 ml) had no impact on PFS with anti-EGFR Rx. Conclusions: We have successfully isolated CTCs from mCRC pts’ blood using Parsortix system. Elevated levels of arginine methylated EGFR is associated with a shorter PFS with anti-EGFR-based Rx. Assessment of meEGFR-CTCs may provide a “liquid biopsy” biomarker for reduced efficacy from anti-EGFR Rx.

Download Full-text

Brain metastases from Truncal and extremity bone and soft tissue sarcoma: Single institution study of oncologic outcomes

Rare Tumors ◽

10.1177/2036361320960060 ◽

2020 ◽

Vol 12 ◽

pp. 203636132096006

Author(s):

Chung Ming Chan ◽

Adam D Lindsay ◽

Andre RV Spiguel ◽

Mark T Scarborough ◽

C Parker Gibbs

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Bone Metastases ◽

Survival Probability ◽

Cerebral Metastasis ◽

Rank Test ◽

Aggressive Treatment ◽

Kaplan Meier ◽

Radium 223 ◽

Cerebellar Metastasis

Brain metastases are a rare occurrence in patients with sarcoma. The prognosis for patients is poor, and treatment can contribute to considerable morbidity. We sought to examine the experience of our institution in managing these patients over a period of 17 years. We performed a retrospective cohort study of patients managed for sarcoma of the extremity or trunk who developed brain metastases from 2000 to 2017. Clinical data were analyzed and we assessed survival outcomes. 14 patients presenting at a mean age of 46.7 years were included. All patients were treated with radiotherapy for their brain metastases. 3 patients underwent surgical excision of their intracranial metastases. Two patients were treated with radium-223 dichloride. Kaplan–Meier survival analysis and the log rank test were used to calculate the survival probability, and to compare patient subgroups. All patients in this study developed lung or bone metastases at a mean interval of 13.3 months prior to the development of brain metastasis. The median interval from diagnosis of a brain metastasis to death was 3.6 months. The Kaplan–Meier survival probability at 6 months was 28.6%, and 14.3% at 1 year. Surgery was not found to be associated with increased survival. Patients with cerebellar metastasis had increased survival probability as compared to those with cerebral metastasis. Patients with extremity or trunk sarcoma who develop brain metastases frequently develop lung or bone metastases in the year preceding their diagnosis of brain metastasis. Patients with cerebellar metastasis may have better survival than those with cerebral metastasis, and an aggressive treatment approach should be considered. Despite aggressive treatment, the prognosis is grim.

Download Full-text

ML-07 High expression of PD-L1 on tumor-associated macrophage is a predictive factor for favorable prognosis in PCNSL

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.070 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii16-ii16

Author(s):

Motomasa Furuse ◽

Hiroko Kuwabara ◽

Naokado Ikeda ◽

Yasuhiko Hattori ◽

Tomotsugu Ichikawa ◽

...

Keyword(s):

Tumor Cells ◽

Tumor Tissue ◽

Central Nervous System Lymphoma ◽

B Cell Lymphoma ◽

Rank Test ◽

Median Percentage ◽

Tumor Associated Macrophage ◽

Kaplan Meier ◽

Coefficient Corrélation ◽

Peritumoral Tissue

Abstract PD-L1 and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we investigated the expressions of PD-L1 and PD-L2 in surgical specimens from needle biopsies and craniotomies to compare tumor tissue with surrounding tumor tissue (peritumoral tissue) and analyzed the correlation between expression of PD-L1/PD-L2 and survival in patients with PCNSL. We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. The tumor cells did not express very much PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95%CI: 0–94.6) than intratumoral macrophages (27.5%; 95%CI: 0–81.1, p=0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p=0.0429), with very low coefficient correlation (ρ=0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p=0.0008; better MSKCC score, p=0.0103; peritumoral macrophages: low proportion of LDH elevation, p=0.0064) and longer OS (for intratumoral macrophages: high PD-L1=60 months, 95%CI=30–132.6; low PD-L1=24 months, 95%CI=11–48; p=0.032; for peritumoral macrophages: high PD-L1=60 months, 95%CI=30.7-NR; low PD-L1=14 months, 95%CI=3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR=0.30, 95%CI=0.12–0.77, p=0.0129). Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL.

Download Full-text

Presence of Epstein-Barr virus in extranodal T-cell lymphomas: differences in relation to site

Blood ◽

10.1182/blood.v83.6.1612.bloodjournal8361612 ◽

1994 ◽

Vol 83 (6) ◽

pp. 1612-1618 ◽

Cited By ~ 1

Author(s):

PC de Bruin ◽

M Jiwa ◽

JJ Oudejans ◽

P van der Valk ◽

P van Heerde ◽

...

Keyword(s):

T Cell ◽

Tumor Cells ◽

Epstein Barr Virus ◽

Large Cell ◽

Differentiation Markers ◽

Similar Morphology ◽

Barr Virus ◽

T Cell Lymphomas ◽

Epstein Barr ◽

Hodgkin's Lymphomas

T-cell lymphomas with similar morphology but with different sites of origin have a different clinical behavior. The theoretical explanation for this finding originates from the hypothesis that non-Hodgkin's lymphomas (NHLs) are neoplastic equivalents of immunological reactions involving tissue-restricted lymphocytes. This hypothesis also implies that T-NHLs originating from different sites differ in their genesis, and thus may differ in oncogen expression, expression of adhesion molecules, or presence of certain DNA/RNA viral sequences. Therefore, we have investigated in T-cell lymphomas with similar morphology originating from different sites, ie, nose (n = 5; all pleomorphic small- or medium- and large-cell T-cell lymphomas [PTL]), skin (PTL, n = 6; anaplastic large-cell [ALCL], n = 11), gut (PTL, n = 8; ALCL, n = 4), and lung (PTL, n = 6), the presence of Epstein-Barr virus (EBV) at the DNA, RNA (EBER 1 and EBER 2), and protein level (LMP-1). A double- staining technique was used to detect EBER 1/2, LMP-1, and differentiation markers at the single-cell level. High numbers of EBER 1/2-positive tumor cells (> 100 per medium power field [mpf]) were found in five of five nasal T-cell lymphomas, none of 17 primary cutaneous T-cell lymphomas, one of 12 gastrointestinal T-cell lymphomas (ALCL), and two of six pulmonary T-cell lymphomas. These lymphomas are therefore called EBV-associated lymphomas. In contrast to our earlier findings in lymph nodes, no extranodal lymphomas were found, with only a few EBV-positive tumor cells. Five gastrointestinal cases positive for EBV by polymerase chain reaction (PCR) showed that EBER 1/2 was only found in sporadic nonneoplastic, ie, reactive lymphocytes. Angiocentricity was present in 18 PTL and one ALCL, but not associated with the presence of EBV. These results indicate that the presence of EBV in extranodal T-cell lymphomas is site-restricted and argues for a different pathogenesis of T-cell lymphomas with similar morphology but originating from different sites. The presence of EBV in most tumor cells in these EBV-associated lymphomas suggests that when present, EBV might be important in the pathogenesis of these lymphomas.

Download Full-text

Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.737794 ◽

2021 ◽

Vol 11 ◽

Author(s):

Junmei Hao ◽

Wenfeng Zhang ◽

Yan Lyu ◽

Jiarui Zou ◽

Yunyun Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Survival Probability ◽

Rank Test ◽

Breast Cancer Patients ◽

Dot Blot ◽

Protein Levels ◽

Kaplan Meier ◽

Combined Use ◽

Surrogate Assay

BackgroundKi67 is a biomarker of proliferation to be used in immunohistochemistry (IHC)-based surrogate assay to determine the necessity of cytotoxic therapy for Luminal-like breast cancer patients. cyclinD1 is another frequently used biomarker of proliferation. A retrospective study was performed here to investigate if these two biomarkers may be combined to improve the prognosis of Luminal-like patients.MethodsBoth Ki67 and cyclinD1 protein levels were measured absolutely and quantitatively using Quantitative Dot Blot method in 143 Luminal-like specimens. Optimized cutoffs for these two biomarkers were developed to evaluate their prognostic roles using Kaplan–Meier overall survival (OS) analysis.ResultscyclinD1 was found as an independent prognostic factor from Ki67 in univariate and multivariate OS analyses. At optimized cutoffs (cyclinD1 at 0.44 μmol/g and Ki67 at 2.31 nmol/g), the subgroup with both biomarkers below the cutoffs (n = 65) had 10-year survival probability at 90% in comparison to those with both biomarkers above the cutoffs (n = 18) with 8-year survival probability at 26% (log-rank test, p <0.0001). This finding was used to modify the surrogate assay using IHC-based cyclinD1 scores, with p-value decreased from 0.031 to 0.00061 or from 0.1 to 0.02, when the Ki67 score of 14 or 20% was used as cutoff, respectively, in the surrogate assay.ConclusionThe current study supports the prospective investigation of cyclinD1 relevance in the clinic.

Download Full-text

Analysis of clinical features of ovarian cancer (OC) and breast cancer (BC) among BRCA-mutated (BRCA+) and sporadic (NH) double tumours.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5548 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5548-5548

Author(s):

Maria Ornella Nicoletto ◽

Marco Rocchetto ◽

Grazia Artioli ◽

Alessandra Perin ◽

Cristina Ghiotto ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Outcome ◽

Rank Test ◽

Chi Square ◽

Exact Test ◽

Kaplan Meier ◽

Genetic Features ◽

Prospective Trials

5548 Background: The clinical outcome of double OC and BC is specifically unknown either BRCA+ and in double tumours NH patients. Methods: The present databases made of 106 patients, 67 cases of NH (negative, no-tested or ongoing test for BRCA1/2 mutations) and 39 of BRCA+, were constituted to identify the clinical and pathological features of BC and OC. The primary endpoint was to evaluate biological characteristics of both cancers and clinical outcome of OC in coexistence with BC. Patients were censored at last follow-up or death (any cause) for determination of overall survival (OS). OS were determined using the Kaplan-Meier method and log-rank test to compared the different levels of a variable. Pearson Chi-Square or Fisher’s exact test were used to compare relationship between variables in to groups and Mann-Whitney U test to compare the medians. Results: 32/39 (82 %) BRCA+ and 44/67 (66 %) NH had BC as their first malignancy. As regards the genetic test on NH patients, 28 were BRCA negative, 22 have not been tested and in 10 patients the test is still in progress. All BRCA2 patients had BC as first malignancy, while 20/22 of BRCA1. Bilateral BC was more frequent in BRCA+ than in NH (33 % vs 9 %), resulted in a fivefold higher risk (p = 0.002). III-IV stage OC at diagnosis was 79% in BRCA+ vs 55 % in NH (p = 0.013); indeed BRCA+ patients have a threefold higher risk (however moderate) to develop an advanced stage OC. Death for progression of ovarian cancer involved both groups, and third neoplasm was involved in death cause in 1/1 of BRCA and 5/6 of NH. Two BRCA1 with OC as first neoplasm are alive. Conclusions: III-IV stage OC is more frequent in BRCA+ than in NH, and the main cause of disease progression and death is due to OC. Eventually the most relevant conclusive assessment is the suggestion of a more conserving management for BC and an intensive follow-up for OC in patients with double tumours, irrespective of their pathological or genetic features. Prospective trials are also indicated.

Download Full-text