Improved prognostication in soft tissue sarcoma: independent information from vascular invasion, necrosis, growth pattern, and immunostaining using whole-tumor sections and tissue microarrays.
In 140 mixed primary soft tissue sarcomas with a median follow-up of 6 years, the prognostic importance of tumor size, tumor depth, grade, necrosis, vascular invasion, and peripheral growth pattern (pushing versus infiltrating) was evaluated on whole-tumor sections. Immunohistochemical expression of Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and P-glycoprotein was determined using tissue microarray from the peripheral growth zone. Local recurrences developed in 17% of the patients and correlated with necrosis, vascular invasion, and cyclin A expression. No local recurrence developed in tumors with a pushing growth pattern, regardless of tumor grade and depth. Metastasis developed in 39% of the patients. Vascular invasion was identified in 36% of the tumors and was the strongest prognostic factor for metastasis with a hazard ratio of 3.5. Growth pattern and tumor necrosis were also strong prognostic factors for metastasis, whereas malignancy grade, tumor size, and tumor depth did not have any independent prognostic value. Immunostaining showed independent prognostic information for Ki-67, beta-catenin, CD44, and P-glycoprotein. The results indicate that whole-tumor sections could facilitate identification of vascular invasion, necrosis, and peripheral growth pattern and that immunohistochemical profiling from the growth zone also provides independent prognostic information for metastasis in soft tissue sarcoma.
Engellau
Jacob
J
Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden. jacob.engellau@onk.lu.se
Bendahl
Pär-Ola
PO
Persson
Annette
A
Domanski
Henryk A
HA
Akerman
Måns
M
Gustafson
Pelle
P
Alvegård
Thor A
TA
Nilbert
Mef
M
Rydholm
Anders
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D019925:Cyclin A / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis; D005260:Female; D016591:Histocytological Preparation Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012509:Sarcoma / Q000473:pathology*; D016019:Survival Analysis; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051176:beta Catenin
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D019925:Cyclin A; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin