Analysis of neuroendocrine differentiation and the p53/BAX pathway in UICC stage III colorectal carcinoma identifies patients with good prognosis

Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated. Methods: SATB2 expression was analysed in 1039 CRCs and correlated with clinicopathological and morphological factors, CDX2 expression as well as survival parameters within the overall cohort and in clinicopathological subgroups. Results: SATB2 loss was a strong prognosticator in univariate analyses of the overall cohort (p < 0.001 for all survival comparisons) and in numerous subcohorts including high-risk scenarios (UICC stage III/high tumour budding). SATB2 retained its prognostic relevance in multivariate analyses of these high-risk scenarios (e.g., UICC stage III: DSS: p = 0.007, HR: 1.95), but not in the overall cohort (DSS: p = 0.1, HR: 1.25). SATB2 loss was more frequent than CDX2 loss (22.2% vs. 10.2%, p < 0.001) and of higher prognostic relevance with only moderate overlap between SATB2/CDX2 expression groups. Conclusions: SATB2 loss is able to identify especially aggressive CRCs in high-risk subgroups. While SATB2 is the prognostically superior immunohistochemical parameter compared to CDX2 in univariate analyses, it appears to be the less sensitive marker for colorectal differentiation as it is lost more frequently.

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The value of neuroendocrine markers for response to therapy and survival in patients with advanced non-small cell lung cancer

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1002037p ◽

2010 ◽

Vol 138 (1-2) ◽

pp. 37-42

Author(s):

Marina Petrovic ◽

Nevenka Ilic ◽

Dejan Baskic

Keyword(s):

Lung Cancer ◽

Pleural Effusion ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Response ◽

Neuroendocrine Differentiation ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Neuroendocrine Markers

Introduction. Non-small cell lung cancer (NSCLC) accounts for about 70-80% of all lung cancers. In comparison with small cell lung cancer, NSCLC has relatively low therapy response. Discovery of neuroendocrine markers within the NSCLC group (10-30%) has initiated the issue of their importance in the therapy and prognosis. Objective. The aim of this study was to determine the influence of neuroendocrine differentiation on treatment response and survival in patients with advanced NSCLC. Methods. A clinical trial included 236 patients (73.7% males), with diagnosis of NSCLC, determined by histological verification. These patients were treated by combined chemo- and X-ray therapy at stage III (without pleural effusion) or chemotherapy only at stage III (with pleural effusion) and stage IV of NSCLC. When the progression had been noted at the stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron-specific enolase (NSE), chromogranin A (ChrA) as well as synapthophysin (SYN) expression in tissue examples was determined by immunohistochemical analysis with monoclonal mouse anti human bodies (DAKO Comp, Denmark). The treatment was conducted during 4 to 6 chemotherapeutic cycles. The efficacy was assessed after the therapy regimen; median survival time was assessed after the randomization. Results. NSE, ChrA and SYN expression were noted in 56 (23.7%), 33 (13.9%) and 39 (16.5%) patients, respectively. Better therapeutic response was significantly higher in patients with expression of NSE, ChrA and SYN (p<0.05). There was significant correlation between therapy response and the percentage of positive tumour cells with neuroendocrine differentiation (p<0.05). The one-year and two-year follow-up survival period in patients with neuroendocrine expression was 64% (without expression 28%; p<0.001) and 30% (p=0.000). Conclusion. Tissue expression of neuroendocrine markers influences greatly a therapeutic response in patients with advanced stage of NSCLC. Better therapeutic response was recorded in patients with positive expression of neuroendocrine markers and higher percentage of positive tumour cells. Median survival time is higher in patients in III or IV stage of NSCLC, when neuroendocrine markers are expressed.

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Validation of the seventh edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging in patients with stage II and stage III colorectal carcinoma: analysis of 2511 cases from a medical centre in Korea

Colorectal Disease ◽

10.1111/j.1463-1318.2011.02625.x ◽

2011 ◽

Vol 13 (8) ◽

pp. e220-e226 ◽

Cited By ~ 28

Author(s):

K. H. Kim ◽

S. S. Yang ◽

Y. S. Yoon ◽

S.-B. Lim ◽

C. S. Yu ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Tnm Staging ◽

Medical Centre ◽

Stage Ii ◽

Stage Iii ◽

Tumor Node Metastasis ◽

Seventh Edition ◽

Node Metastasis ◽

American Joint Committee ◽

Cancer Tumor

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Folinic acid modulated bolus 5-FU or infusional 5-FU for adjuvant treatment of patients of UICC stage III colon cancer: Preliminary analysis of the PETACC-2-study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3563 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 3563-3563 ◽

Cited By ~ 5

Author(s):

A. Carrato ◽

C. Köhne ◽

L. Bedenne ◽

I. Popov ◽

O. Bouche ◽

...

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Lymphatic Invasion ◽

Hazard Ratio ◽

Stage Iii ◽

High Dose ◽

Uicc Stage ◽

Stage Iii Colon Cancer ◽

Hand Foot Syndrome ◽

Grade 3

3563 Background: Patients with stage III colon cancer have a high risk for recurrence. Infusional 5-FU may be more active than bolus application. Methods: From 01/1997 to 03/2004 a total of 1601 patients with UICC stage III colon cancer were randomized to receive the Mayo-Clinic regimen or infusional 5-FU either the weekly high dose AIO regimen, the bi-weekly LV5FU2 regimen or the Spanish weekly high dose TTD-regime. The major aim of this study was to demonstrate a difference of 7 % in the 5 year survival rate in favour of the infusional arm for which a total of 424 events were required. Results: After a median follow-up of 31 months 478 events have occurred. 804 patients received the standard arm and 797 the experimental arm (AIO N=331, EORTC N=92, FFCD N=211, TTD N=163). The median age was 64 years; patients were well distributed according to TNM-category (T3 73 vs. 75%, T4 17 vs. 16%, N2 31 vs. 34%), vascular and lymphatic invasion and grading. The bolus regimen induced a higher rate of grade 3 or 4 leukopenia (7.1% versus 2.0%), stomatitis grade 3 or 4 (9.8% versus 3.3%) or diarrhea grade 3 or 4 (16% vs. 15%). Hand-Foot-Syndrome was more frequent in the experimental arm (4.4% versus 0.4%). There was no difference in the recurrence free survival at 5 years (57% versus 56%; hazard ratio 1.00, 95% CI, 0.84 to 1.21; P=0.9) or overall survival at 5 years 71% versus 72%; hazard ratio 0.91, 95% CI, 0.71 to 1.16; P=0.44). Conclusions: Infusional 5-FU does not improve RFS or overall survival of stage III colon cancer compared to the Mayo regimen but is less toxic. Supported by Deutsche Krebshilfe No significant financial relationships to disclose.

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Grading lymph node metastasis: a feasible approach for prognostication of patients with stage III colorectal cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2014-202772 ◽

2015 ◽

Vol 68 (9) ◽

pp. 742-745 ◽

Cited By ~ 1

Author(s):

Annika Resch ◽

Lars Harbaum ◽

Marion J Pollheimer ◽

Peter Kornprat ◽

Richard A Lindtner ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Metastatic Lymph Node ◽

Tumour Size ◽

Primary Tumour ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Stage Iii ◽

Uicc Stage ◽

Cancer Specific Survival

This study aimed to assess the clinicopathological significance of tumour differentiation of metastatic lymph node tissue in patients with American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III colorectal cancer. In a cohort of 145 patients, lymph node grades were G1 in 77 (53.1%), G2 in 41 (28.3%) and G3 in 27 (18.6%) cases, respectively. Despite differences in 77 (53.1%) cases, primary tumour and lymph node grade correlated significantly (Somer's D=0.639; p<0.001). Lymph node grade was significantly associated with N classification (p=0.009), tumour size (p=0.024) and lymphovascular invasion (p=0.004). Patients with lymph node grade G1 had better progression-free survival (p=0.031) and cancer-specific survival (p=0.008). Multivariable analysis identified lymph node grade as independent predictor of cancer-specific survival in this cohort. In conclusion, lymph node grade emerged as a promising novel prognostic variable for patients with AJCC/UICC stage III disease. Additional studies are warranted to validate this new finding.

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Incidence and Prognostic significance of Signet Ring Cell Histology in Gastric Cancer. A cross sectional study from Turkey: Pure Signet Ring Cell Histology in Gastric Cancer

10.32592/ircmj.2020.22.9.34 ◽

2020 ◽

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Poor Prognosis ◽

Prognostic Significance ◽

Good Prognosis ◽

Signet Ring Cell ◽

Stage I ◽

Stage Iii ◽

Signet Ring ◽

Ring Cell

Purpose: The present study aims to evaluate the incidence of signet ring cell (SRC) histology in patients with gastric cancer and its prognostic significance on the disease stage. Methods: Between November 2006 and September 2019, 309 patients were reviewed retrospectively in Kartal Koşuyolu High Specialization Training and Research Hospital Gastroenterology Surgery clinic in Turkey and the clinicopathological features and survival status were examined in the presence of ring cell histology. Results: Of the patients, 71.4% had gastric cancer with a non-SRC histology and 28.6% had an SRC histology. The presence of an SRC histology was found to be associated with young age (p=0.007), advanced depth of wall invasion (p=0.001), number of positive lymph nodes (p=0.022) and presence of vascular invasion (p=0.044). The presence of an SRC histology was associated with good prognosis in patients with stage I gastric cancer (p=0.045), but with poor prognosis in patients with stage III disease (p=0.034). The study found no significant association between stage II disease and overall survival. Conclusions: The present study found survival to be associated with good prognosis in stage I, and poor prognosis in stage III among patients with gastric cancer with SRC histology. No prognostic significance could be established for overall survival.

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Interim results of the phase I/II study of trabedersen (AP 12009) in patients with pancreatic carcinoma, malignant melanoma, or colorectal carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4619 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4619-4619 ◽

Cited By ~ 3

Author(s):

H. Oettle ◽

A. Hilbig ◽

T. Seufferlein ◽

R. M. Schmid ◽

T. Luger ◽

...

Keyword(s):

Malignant Melanoma ◽

Colorectal Carcinoma ◽

Pancreatic Carcinoma ◽

Phase Ii ◽

Stable Disease ◽

Phase Ii Study ◽

Stage Iii ◽

Primary Study ◽

Tgf Beta ◽

Beta 2

4619 Background: TGF-beta 2 is one of the most potent immunosuppressors and mediates escape from immunosurveillance. It also plays a crucial role in tumor progression by regulating metastasis, angiogenesis, and proliferation. Trabedersen, a TGF-beta 2-specific inhibitor has already shown a clear survival benefit in a randomized active-controlled phase II study in high-grade glioma patients, compared to standard chemotherapy. Methods: 33 patients with advanced pancreatic carcinoma (stage IVA/IVB) (N=23), malignant melanoma (stage III/IV) (N=5) or colorectal carcinoma (stage III/IV) (N=5) were treated with trabedersen as 2nd-4th-line treatment. Two treatment schedules (1st schedule:7d on, 7d off; 2nd schedule: 4d on, 10d off; up to 10 cycles) were evaluated in a cohort dose-escalation design. Primary study objective: maximum tolerated dose (MTD); secondary objectives: safety and tolerability, pharmacokinetics and antitumor activity. Results: Patient recruitment for both schedules is completed. Very good safety and tolerability of trabedersen was observed, with moderate thrombocytopenia as main adverse event. Max. grade 3 dose-limiting toxicities (2 thrombocytopenias, 1 exanthema) occurring with 240 mg/m2/d in the 1st schedule established the MTD at 160 mg/m2/d. MTD has not been reached in the 2nd schedule. Of the 5 melanoma patients one from the 1st schedule showed stable disease and lived for 13.8 months; 3 patients from the 2nd schedule are still alive. Median overall survival (mOS) for pancreatic carcinoma patients in the 1st schedule was 6.8 months. One pancreatic carcinoma patient showed a complete response and is alive 38 months after trabedersen therapy. Current mOS for pancreatic carcinoma patients in cohort 1 (N=5) of the 2nd schedule is 13.2 months; 2 of these patients are alive, one with stable disease 14.8 months after begin of trabedersen treatment. Conclusions: Trabedersen has a very good safety and tolerability profile. The survival data are very encouraging. The study will continue with one dose in at least 12 patients. A randomized, active-controlled phase II study compared to standard therapy in patients with pancreatic carcinoma is in preparation; another one in malignant melanoma is being planned. [Table: see text]

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