Fig 1.
Histopathological features of colorectal GEP-NEN.
A: Quantification of histological grading of NEN of the colon and rectum according to WHO criteria. B: Quantification of metastatic behavior of colorectal NEN with respect to histological grading. G1:14 M1 vs. 18 M0; G2: 9M1 vs. 3 M0 and G3 15 M1 vs. 0 M0 cases; M1: metastasis; M0: no metastasis. C and D: Quantification of immunohistochemical CgA (n = 44) and synaptophysin (n = 42) staining in patients with colorectal NEN. The expression levels include “negative” (no visible staining), “weakly or focally positive” (up to 30% positive tumor cells), “positive” (30 to 75% positive tumor cells), and “highly positive” (more than 75% strongly positive tumor cells) staining.
Fig 2.
Immunohistochemistry in colorectal and intestinal NEN.
Representative histological sections of well-differentiated (G1 and G2) neuroendocrine tumors and poorly differentiated colorectal NEN (A) and well-differentiated (G1) NET of the small bowel (B) are displayed after immunohistochemical staining for CgA and synaptophysin.
Table 1.
Clinical characteristics of 62 evaluated patients with NEN of the colon and rectum.
Fig 3.
Maximum levels of tumor markers tested in patients with colorectal NEN.
Maximum plasma levels ever measured at our hospital for the individual GEP-NEN patients for CgA (n = 59), serotonin (n = 42), urine elimination of 5-HIAA (n = 39), CEA (n = 29) and CA19-9 (n = 21) are displayed (A). Representative evaluations of CgA, Serotonin and CA19-9 in consideration of metastatic disease are shown in Fig 3B. The red lines represent the cutoff levels for significant elevation of the individual tumor markers (CgA (50 U/l), serotonin (450 ng/ml) and CA19-9 (27U/ml)).
Fig 4.
Plasma CgA levels in patients with confirmed tumor progression.
Matched pairs of plasma CgA are shown before (timepoint 1) and after (timepoint 2) a confirmed tumor progression in patients with colorectal NEN (A, n = 20) and with NEN of the small bowel (B, n = 18). CT or MRI scans confirmed tumor progression according to RECIST criteria. The interval of tumor progression ranges from six to twelve months.
Fig 5.
Survival rates of patients with colorectal NEN.
A: A Kaplan-Meier plot displays the overall survival of 56 patients with colorectal NEN (median OS colon 4.0 years and 8.5 years for rectum). B: A Kaplan-Meier plot shows the survival analysis of three different subgroups based on grading who differ in their prognosis: The first group (30 patients, blue line, G1 tumor, Ki67: <2%, median OS not reached (n.r.)), the second group (11 patients, green line, G2 tumor, Ki67: ≤20%, median OS 4.5 years) displayed an intermediate prognosis and the third group (14 patients, red line, G3 tumor, Ki67: >20%) exhibits the worst prognosis with a median OS of 2.5 years.