P105 as a prognostic indicator in patients irradiated for locally advanced head-and-neck cancer: a clinical/laboratory correlative analysis of RTOG-9003.
OBJECTIVE
In a previous retrospective study, p105 AD, a proliferation-associated nuclear antigen density (AD), was found to be an independent prognostic factor for patients irradiated for locally advanced head-and-neck cancer. We sought to confirm this finding by analyzing patients entered on RTOG 9003, a Phase III randomized trial of altered fractionation radiotherapy.


METHODS
Paraffin blocks of pretreatment biopsies of the primary tumor of patients with Stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, or supraglottic larynx, or Stage II squamous cell carcinoma of the hypopharynx or base of tongue entered on RTOG 9003 were prospectively collected at patient entry. From these paraffin blocks, areas of tumor were selected based on histologic examinations and sectioned. Nuclear suspensions were then prepared and processed for p105 antibody and DNA staining. Flow cytometric quantification of p105 labeling indices and DNA content were then performed for correlation with local-regional control and survival.


RESULTS
Paraffin blocks of tumor biopsies from 457 of 1073 patients entered were available for p105 determination. There was no significant difference in pretreatment characteristics between patients who had paraffin blocks available or not available. The median (range) of p105 labeling index (LI-C), p105 labeling index of cells in S phase (p105 LI-S), and p105 AD were 56 (range: 6-99), 8.255 (range: 0.913-23), and 67 (range: 5-364), respectively. Multivariate analysis of prognostic factors showed that T stage, N stage, Karnofsky performance status, and fractionation schedule were significant for local-regional control (p < 0.0001, 0.0011, <0.0001, and 0.007, respectively) and T stage, N stage, Karnofsky performance status, and tumor grade were significant for survival (p = 0.018, 0.002, <0.0001, and 0.0058, respectively). Neither p105 LI-C nor p105 LI-S nor p105 AD nor DNA ploidy was significant for local-regional control or survival.


CONCLUSIONS
p105 labeling indices, antigen density, and DNA ploidy do not predict the outcome of patients irradiated for advanced squamous cell carcinomas of the head and neck.
Hammond
E
E
LDS Hospital, Salt Lake City, UT 84143, USA. idehammo@ihc.com
Berkey
Brian A
BA
Fu
Karen K
KK
Trotti
Andy
A
Meredith
Ruby F
RF
Jones
Christopher U
CU
Byhardt
R
R
Horwitz
E M
EM
Ang
K Kian
KK
D000951:Antigens, Neoplasm / Q000032:analysis*; D034961:Antigens, Nuclear / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology / Q000532:radiotherapy*; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis*; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D009062:Mouth Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D010610:Pharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D011379:Prognosis; D011859:Radiography
D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; C478629:P105 antigen, human