The prognostic value of bone marrow retention index and bone marrow-to-liver ratio of baseline 18F-FDG PET/CT in diffuse large B-cell lymphoma.

OBJECTIVE: To determine prognostic value of bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) measured on baseline dual-phase 18F-FDG PET/CT in a series of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated homogeneously with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 135 patients with newly diagnosed DLBCL. All patients underwent dual-phase 18F-FDG PET/CT. The following PET parameters were calculated for both tumor and bone marrow: maximum standardized uptake value (SUVmax) at both time points (SUVmax early and SUVmax delayed), SUVmax increment (SUVinc), RI, and BLR. Patients were treated with R-CHOP regimen and response at end of treatment was assessed. RESULTS: The final analysis included 98 patients with complete remission. At a median follow-up of 22 months, 57 patients showed no relapse, 74 survived, and 24 died. The 2-year relapse-free survival (RFS) values for patients with higher and lower RI-bm were 20% and 65.1%, respectively (p < 0.001), and for patients with higher and lower BLR were 30.2% and 69.6%, respectively (p < 0.001). The 2-year overall survival (OS) values for patients with higher and lower RI-bm were 60% and 76.3%, respectively (p = 0.023), and for patients with higher and lower BLR were 57.3% and 78.6%, respectively (p = 0.035). Univariate analysis revealed that RI-bm and BLR were independent significant prognostic factors for both RFS and OS (hazard ratio [HR] = 4.02, p < 0.001, and HR = 3.23, p < 0.001, respectively) and (HR = 2.83, p = 0.030 and HR = 2.38, p = 0.041, respectively). CONCLUSION: Baseline RI-bm and BLR were strong independent prognostic factors in DLBCL patients. CLINICAL RELEVANCE STATEMENT: Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) could represent suitable and noninvasive positron emission tomography/computed tomography (PET/CT) parameters for predicting pretreatment risk in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. KEY POINTS: • Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) are powerful prognostic variables in diffuse large B-cell lymphoma (DLBCL) patients. • High BLR and RI-bm are significantly associated with poor overall survival (OS) and relapse-free survival (RFS). • RI-bm and BLR represent suitable and noninvasive risk indicators in DLBCL patients.

MIR-379-5p Expression in Endometrial Cancer and Its Correlation with ROR1 Expression.

OBJECTIVE: To asses miR-379-5p expression in endometrial cancer (EC) and its correlation with ROR1 expression and to investigate the relation between miR-379-5p and ROR1 expressions and the clinicopathological picture of EC. METHODS: Fifty female of EC were joined to this study. The gene expression of miR-379-5p (by quantitative real time-PCR) and ROR1 (by quantitative real time-PCR and immunohistochemistry) were studied in EC and normal nearby endometrial tissue. RESULTS: The gene expression of miR-379-5p was significantly downregulated while that of ROR1 was significantly upregulated in EC tissues compared to adjacent normal endometrial tissues. Furthermore, miR-379 and ROR1 expressions significantly associated with tumor stage (P< 0.045), grade (P< 0.001), myometrial invasion (P <0.001) and LN metastasis (P< 0.034). In addition, miR-3795p and ROR1 gene expression were negatively correlated (r = -0.746, P < 0.001). CONCLUSIONS: In EC, miR-379-5p can be used as a diagnostic marker, and ROR1 could be a potential target of miR-379-5p.

Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer.

The potentiation and activation of Wnt signaling pathways are now assumed to mediate the self-renewal and proliferation of colon cancer stem cells that are responsible for therapeutic resistance, tumor relapse, and metastasis. We aimed to evaluate LGR5, Prox1, and Notch1 immunohistochemical expression in stage II to III colon cancer. Their predictive role of tumor relapse, overall survival, and disease-free survival was statistically analyzed. Our results revealed that high LGR5 expression was identified in 56.7% of the patients, LGR5 expression was significantly associated with left-sided tumors (P<0.001). Moreover, its expression was significantly associated with the unfavorable tumor characteristics including high grade, deep invasion (pT), lymph node metastasis, and advanced tumor stage (P<0.001 for each). High Prox1 expression was observed in 65% of the cases, and its expression was significantly associated with tumor grade, lymph node metastasis, and the advanced tumor stage (P=0.004, 0.009, 0.016, respectively). Positive Notch1 expression was identified in 35% of patients, and it was inversely associated with high grade lymph node metastasis, deep invasion (pT), and advanced tumor stage (P<0.001 for each). During the follow-up period, the tumor relapse was significantly associated with high LGR5, high Prox1, and negative Notch1 expression. Shorter overall survival and disease-free survival were significantly associated with high LGR5, high Prox1, and negative Notch1 expression. High LGR5, high Prox1, and negative Notch1 expression are unfavorable prognostic factors in colon cancer. Prox1 is a crucial regulator of Notch-independent LGR5+ stem cells that is mostly responsible for relapse and therapeutic resistance in stage II to III colon cancer.

ERCC1, PARP-1, and AQP1 as predictive biomarkers in colon cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The recognition of high-risk colon cancer patients prone to chemoresistant and recurrent disease is a challenge. OBJECTIVES: We aimed to assess the immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy. Their predictive role of tumor progression and disease-free survival (DFS) was analyzed. METHODS: The immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy was studied. The collected data on the overall survival (OS), disease-free survival (DFS), and the response to the chemotherapy were analyzed. RESULTS: Positive nuclear ERCC1 expression was identified in 58.3% of the patients, ERCC1 expression was significantly associated with left-sided tumors (P< 0.01). Moreover, its expression was significantly associated with the aggressive tumor characteristics including high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). High nuclear PARP-1 expression was observed in 63.3% of the cases, and its expression was significantly associated with tumor grade and lymph node metastasis (P= 0.003 for each). Positive membranous AQP1 expression was identified in 41.7% of patients, and it was associated with high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). During the follow-up period, 23 patients (38.3%) exhibited a tumor progression; this was significantly associated with positive ERCC1, high PARP-1, and negative AQP1 expression. Statistics of the survival data revealed that shorter DFS was significantly associated with positive ERCC1, high PARP-1, and positive AQP1 expression (P= 0.005, 0.016, 0.002, respectively). CONCLUSIONS: ERCC1, PARP1, and AQP1 are adverse prognostic biomarkers in stage II-III colon cancer. Moreover, adjuvant chemotherapy may not be beneficial for patients with positive ERCC1, high PARP1, and AQP1-negative tumors. Therefore, we recommend that ERCC1, PARP-1, and AQP1 should be assessed during the selection of the treatment strategy for stage II-III colon cancer patients.

Fatty acid synthase, Her2/neu, and E2F1 as prognostic markers of progression in non-muscle invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease which has an unpredictable risk of progression to muscle-invasive bladder cancer (MIBC). The selection of patients who may benefit from early radical intervention is a challenge. To define the useful prognostic markers for progression, we analyzed the immunohistochemical expression of fatty acid synthase (FASN), Her2/neu, and E2F1 in 60 cases of NMIBC who underwent TURBT and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Their predicting role for tumor recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS) was analyzed. High FASN expression was observed in 56.7% (34/60) of NMIBC cases, and FASN expression was significantly associated with the tumor size, grade, and tumor stage (p = 0.003, p < 0.001, p < 0.0001 respectively). Positive Her2/neu was noted in 18.3% (11/60) of the cases, and its expression was significantly associated with the tumor size, histologic grade, and tumor stage (p = 0.001, p = 0.002, p = 0.011 respectively). High E2F1 expression was detected in 40% of the cases, and it was associated with tumor size, histologic grade, and tumor stage (p < 0.001 for each). Analysis of follow-up period revealed that NMIBC with high FASN, positive Her2/neu, and high E2F1 expression exhibited a potent relation with tumor progression, shorter RFS, and poor PFS. Conclusions: High FASN, Her2/neu, and E2F1 are considered as adverse prognostic factors of tumor recurrence and progression in NMIBC and these patients should be followed carefully. Therefore, we suggest that FASN, Her2/neu, and E2F1 should be considered and evaluated during the selection of the appropriate management strategy for NMIBC patients.