Prospective randomized study comparing sentinel lymph node evaluation with standard pathologic evaluation for the staging of colon carcinoma: results from the United States Military Cancer Institute Clinical Trials Group Study GI-01.
BACKGROUND
The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial.


OBJECTIVE
This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer.


METHODS
Between August 2002 and April 2006 we randomly assigned 161 patients with stage I-III colon cancer to standard histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1% isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with standard histopathology. SLN-positive disease was defined as individual tumor cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC. Primary end point was the rate of nodal upstaging.


RESULTS
Significant nodal upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%, P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no statistically significant difference in node-positive rate was apparent between the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56) nodal upstaging was identified by evaluation of H&E stained step sections of SLNs among study arm patients who would have otherwise been staged node-negative (N0) by conventional pathologic assessment alone.


CONCLUSIONS
SLN mapping, step sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease and improves staging in patients with resectable colon cancer. A prospective trial is ongoing to determine the clinical significance of colon cancer micrometastasis in sentinel lymph nodes.
Stojadinovic
Alexander
A
Department of Surgery, Division of Surgical Oncology, and United States Military Cancer Institute, Walter Reed Army Medical Center, 6900 Georgia Avenue N.W., Washington, D.C. 20307, USA. alexander.stojadinovic@na.amedd.army.mil
Nissan
Aviram
A
Protic
Mladjan
M
Adair
Carol F
CF
Prus
Diana
D
Usaj
Slavica
S
Howard
Robin S
RS
Radovanovic
Dragan
D
Breberina
Milan
M
Shriver
Craig D
CD
Grinbaum
Ronit
R
Nelson
Jeffery M
JM
Brown
Tommy A
TA
Freund
Herbert R
HR
Potter
John F
JF
Peretz
Tamar
T
Peoples
George E
GE
D000368:Aged; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000473:pathology*; D004396:Coloring Agents; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012394:Rosaniline Dyes; D021701:Sentinel Lymph Node Biopsy; D016896:Treatment Outcome; D014481:United States
D004396:Coloring Agents; D012394:Rosaniline Dyes; C025484:iso-sulfan blue; D007633:Keratins