Histopathological tumor invasion of the mesenterico-portal vein is characterized by aggressive biology and stromal fibroblast activation.
Mesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology.



Patients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database. Immunohistochemical staining of tumor tissue was performed for the markers of epithelial-mesenchymal transition (EMT) E-Cadherin, Vimentin and beta-Catenin. Morphology of cancer-associated fibroblasts (CAFs) was assessed as inactive or activated. Statistical calculations were performed with MedCalc software.



In total, 41 patients could be included. Median overall survival was 25 months. PVI was found in 17 patients (41%) and was significantly associated with loss of membranous E-Cadherin in tumor buds (p = 0.020), increased Vimentin expression (p = 0.03), activated CAF morphology (p = 0.046) and margin positive resection (p = 0.005).



Our findings suggest that PVI is associated with aggressive tumor biology and disseminated growth less amenable to margin-negative resection.
Clinic for General and Visceral Surgery, University Medical Center Freiburg, Germany; Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany.
Hryhoriy
H
Lapshyn
Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany.
Louisa
L
Bolm
Institute of Surgical Pathology, University Medical Center Freiburg, Germany.
Ilona
I
Kohler
Institute of Surgical Pathology, University Medical Center Freiburg, Germany; Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany; German Cancer Consortium (DKTK) and Cancer Research Center (DKFZ), Heidelberg, Germany.
Martin
M
Werner
Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany.
Franck G
FG
Billmann
Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany.
Dirk
D
Bausch
Clinic for General and Visceral Surgery, University Medical Center Freiburg, Germany; Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany. Electronic address: ulrich.hopt@uniklinik-freiburg.de.
Ulrich T
UT
Hopt
Clinic for General and Visceral Surgery, University Medical Center Freiburg, Germany; Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany.
Frank
F
Makowiec
Clinic for General and Visceral Surgery, University Medical Center Freiburg, Germany.
Uwe A
UA
Wittel
Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany.
Tobias
T
Keck
Institute of Surgical Pathology, University Medical Center Freiburg, Germany; Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany; German Cancer Consortium (DKTK) and Cancer Research Center (DKFZ), Heidelberg, Germany.
Peter
P
Bronsert
Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany.
Ulrich F
UF
Wellner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016208:Databases, Factual; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D008297:Male; D008642:Mesenteric Veins / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011169:Portal Vein / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D014746:Vimentin / Q000032:analysis; D051176:beta Catenin / Q000032:analysis
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D014746:Vimentin; D051176:beta Catenin