Objective:
Carbohydrate antigen 19-9 (CA19-9) is a prognostic marker for patients with pancreatic cancer (PC), but its value as a treatment biomarker is unclear.
Summary Background Data:
Although CA19-9 is an established prognostic marker for patients with PC, it is unclear how CA19-9 monitoring should be used to guide multimodality treatment and what level of change in CA19-9 constitutes a meaningful treatment response.
Methods:
CA19-9 measurements at diagnosis (pretx), after completion of all planned neoadjuvant therapy (preop), and after surgery (postop) were analyzed in patients with localized PC who had an elevated CA19-9 (≥35 U/dL) at diagnosis. Patients were classified by: 1) quartiles of pretx CA19-9 (Q1-4); 2) proportional changes in CA19-9 (ΔCA19-9) after the completion of neoadjuvant therapy; 3) normalization (CA19-9 <35 U/dL) of preop CA19-9; and 4) normalization of postop CA19-9.
Results:
Among 131 patients, the median overall survival (OS) was 30 months; 68 months for the 33 patients in Q1 of pretx CA19-9 (<80 U/dL) compared with 25 months for the 98 patients in Q2-4 (P = 0.03). For the 98 patients in Q2-4, preop CA19-9 declined (from pretx) in 86 (88%), but there was no association between the magnitude of ΔCA19-9 and OS (P = 0.77). Median OS of the 98 patients who did (n = 29) or did not (n = 69) normalize their preop CA19-9 were 46 and 23 months, respectively (P = 0.02). Of the 69 patients with an elevated preop CA19-9, 32 (46%) normalized their postop CA19-9. Failure to normalize preop or postop CA19-9 was associated with a 2.77-fold and 4.03-fold increased risk of death, respectively (P < 0.003) as compared with patients with normal preop CA19-9.
Conclusions:
Following neoadjuvant therapy, normalization of CA19-9, rather than the magnitude of change, is the strongest prognostic marker for long-term survival.
Summary The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was&found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.
Among patients with localized PC who received neoadjuvant therapy and surgery, the benefit of adjuvant therapy was limited to those with node-positive disease.
Summary Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known as uPAR. In this study, uPA and uPAR levels were semiquantitated by immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD-UK 1, uPA was detected both in stromal and in malignant cells. However, the predominant location was in the stromal cells. Using double-staining, cells containing uPA were also found to coexpress either cytokeratin (an epithelial cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle-or macrophage-like stromal cells, especially when these cells surrounded invasive breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA levels in both stromal and epithelial cells were significantly correlated with those for uPAR. We conclude that both uPA and its receptor are mostly present in stromal cells in invasive breast carcinomas. These results suggest that stromal cells collaborate with malignant cells to mediate metastasis.
Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.