Tumor Biol. DOI 10.1007/s13277-015-4626-1
ORIGINAL ARTICLE
Prognostic value of ABO blood group in patients with early stage cervical cancer treated with radical hysterectomy with pelvic node dissection Jitti Hanprasertpong 1 & Ingporn Jiamset 1 & Thiti Atjimakul 1
Received: 3 November 2015 / Accepted: 10 December 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015
Abstract This study aimed to evaluate the prognostic value of ABO blood groups in early-stage cervical cancer patients. The cohort included 413 patients diagnosed with stages IA2– IB1 cervical cancer who received a radical hysterectomy between 2002 and 2014. The 5-year recurrence-free survival (RFS) and overall survival (OS) were 93.13 and 96.81 % for blood group O, 87.68 and 88.22 % for blood group A, 81.66 and 89.40 % for blood group B, and 83.12 and 94.12 % for blood group AB groups, respectively. Patients were stratified for analysis as either blood group O or non-O. The 5-year RFS and OS were 93.13 and 96.81 % for blood group O and 83.66 and 89.76 % for blood group non-O, respectively. In multivariate analysis, age (P = 0.025), histology (P = 0.020), and deep stromal invasion (P = 0.006) were independent adverse prognostic factors for RFS, while the statistically significant independent prognostic factors for OS were age (P = 0.007) and parametrial involvement (P < 0.001). The Cox model did not show any significant effects of non-O blood group on survival outcome. However, a time-varying-effect Cox model revealed that the non-O blood group was associated with a worse RFS (hazard ratio (HR) 2.69, 95 % confidence interval (95%CI) 1.12–6.46, P = 0.017) and OS (HR 3.13, 95%CI 0.88–11.16, P = 0.053) during the first 5 years. These findings suggest that early-stage cervical cancer patients with a non-O blood group have poorer RFS than the O blood group, which is evidence during the first 5 years.
* Jitti Hanprasertpong
[email protected] 1
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
Keywords Cervical cancer . Radical hysterectomy . ABO blood group . Prognosis . Survival
Introduction Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer mortality among women in developing countries including Thailand. There were an estimated 527,600 new cervical cancer cases and 265,700 deaths worldwide in 2012 [1]. For early-stage cervical cancer, the most common treatment is radical hysterectomy with pelvic lymph node dissection. The primary alternative treatment is radiation therapy, which is usually given in combination with platinum-based chemotherapy. Despite improvement of surgical techniques and better patient selection, the 5-year recurrence-free survival (RFS) rate of early-stage cervical cancer after radical hysterectomy remains approximately 87.7 % [2]. The major clinicopathological factors that predict overall survival (OS) and RFS in patients with early stage cervical cancer after radical hysterectomy have been well elucidated, including histological cell type, tumor size, deep stromal invasion (DSI), lymphovascular space invasion (LVSI), and lymph node status [2, 3]. Although intensive studies for prognostic factors for cervical cancer have been conducted, including in the fields of immunohistochemistry and molecular biology [3–5], identification of additional novel biomarkers is expected to be useful for individualized patient counseling and could improve the prognosis of patients and provide more personalized treatment. The ABO blood group antigens (i.e., A, B, and H antigens), discovered more than one century ago, are complex carbohydrate molecules expressed on the extracellular surface of red blood cell membranes and several other tissue types, including cells from the cervical tissue [6–11]. The synthesis of blood
Tumor Biol. Table 1
Associations of ABO blood group and blood type in clinicopathologic variables in 413 patients
Variable
O Age (year) - 2
124 (76.5) 38 (23.5)
64 (63.4) 37 (36.6)
76 (59.8) 51 (40.2)
14 (60.9) 9 (39.1)
124 (76.5) 38 (23.5)
154 (61.3) 97 (38.7)
Histology - SCC
88 (54.3)
61 (60.4)
79 (62.2)
14 (60.9)
88 (54.3)
154 (61.3)
- AD - ADS
62 (38.3) 7 (4.3)
31 (30.7) 7 (6.9)
38 (29.9) 6 (4.7)
5 (21.7) 4 (17.4)
62 (38.3) 7 (4.3)
74 (29.5) 17 (6.8)
5 (3.1)
2 (2.0)
4 (3.2)
0
5 (3.1)
6 (2.4)
116 (71.6) 46 (28.4)
182 (72.5) 69 (27.5)
127 (78.4) 35 (21.6)
177 (70.5) 74 (29.5)
- 42–50 - >50 FIGO stage - 1A2 - 1B1
- Other LVSI - No - Yes
63 (25.0)
0.010
Tumor size (cm)
0.835
0.014
0.001
0.272
0.227
0.982
0.841
116 (71.6) 46 (28.4)
72 (71.3) 29 (28.7)
93 (73.2) 34 (26.8)
17 (73.9) 6 (26.1)
127 (78.4) 35 (21.6)
69 (68.3) 32 (31.7)
92 (72.4) 35 (27.6)
16 (69.6) 7 (30.4)
153 (94.4)
99 (98.0)
124 (97.6)
21 (91.3)
153 (94.4)
244 (97.2)
- Yes Node metastasis - No - Yes Surgical margin
9 (5.6)
2 (2.0)
3 (2.4)
2 (8.7)
9 (5.6)
7 (2.8)
158 (97.5) 4 (2.5)
93 (92.1) 8 (7.9)
120 (94.5) 7 (5.5)
21 (91.3) 2 (8.7)
158 (97.5) 4 (2.5)
234 (93.2) 17 (6.8)
- Free - Not free Adjuvant therapy - No
154 (95.1) 8 (4.9)
99 (98.0) 2 (2.0)
123 (96.9) 4 (3.1)
20 (87.0) 3 (13.0)
154 (95.1) 8 (4.9)
242 (96.4) 9 (3.6)
125 (77.2)
80 (79.2)
98 (77.2)
17 (73.9)
125 (77.2)
195 (77.7)
37 (22.8)
21 (20.8)
29 (22.8)
6 (26.1)
37 (22.8)
56 (22.3)
DSI - No - Yes PI - No
- Yes
P value
0.302
0.076
0.220
0.155
0.199
0.052
0.094
0.499
0.949
0.900
FIGO The International Federation of Gynecology and Obstetrics, SCC squamous cell carcinoma, AD adenocarcinoma, ADS adenosquamous cell carcinoma, LVSI lymph vascular space invasion, DSI deep stroml invasion, PI parametrial involvement
group ABH antigens is under genetic control where the primary gene products are glycosyltranferases. The ABO gene on chromosome 9q34 encodes glycosyltranferases that catalyze the transfer of nucleotide donor sugars to the H antigen and form the ABO blood group antigens [10, 11]. In 1953, Aird et al. reported an association between ABO blood group and cancer risk in stomach cancer patients, where blood group A was associated with increased risk of stomach cancer [12]. Since that study, the relationship between ABO blood group and incidence, clinicopathologic characteristics, and prognosis has been shown in various human malignancies
such as bladder [13], breast [14], colon [10], esophagus [15, 16], nasopharyngeal [17], pancreatic [18], and ovarian cancers [19], but not as consistently. The mechanisms of cancer development and progression as related to ABO blood group remain unclear. Previous studies have suggested that cervical cancer is highly prevalent among individuals of blood type A [20, 21], while another study reported that blood type B was significantly associated with cervical cancer [22]. Very little is known about the correlation between the oncological outcome of cervical cancer and ABO blood group [23]. To the best of
Tumor Biol. Fig. 1 a Recurrence-free survival of early stage cervical cancer patients by ABO blood groups (O, A, B, and AB). b Overall survival of early stage cervical cancer patients by ABO blood groups (O, A, B, and AB)
our knowledge, only one Italian study has addressed the prognostic impact of ABO blood group on cervical cancer. In this study of 639 patients with cervical cancer, patients with blood type O were associated with a survival time of little better than 5 years, while a 10-year or longer survival was associated with patients with blood type A [23]. Therefore, the aims of this retrospective analysis were to evaluate the relationship between ABO blood group (especially blood type O) and RFS and OS, and to investigate the correlation of ABO blood group with clinicopathological characteristics in a large cohort of early-stage cervical cancer patients who had undergone radical hysterectomy with pelvic lymph node dissection as their primary treatment at Songklanagarind Hospital, the largest tertiary care institute in Southern Thailand.
Material and methods Ethics statement and patients The study was reviewed and approved by the Human Ethics Committee of the Faculty of Medicine, Prince of Songkla
University, and individual informed consent was waived given the anonymous analysis of routine data. Initial enrollment included all patients treated by radical hysterectomy with pelvic lymph node dissection for cervical cancer stages IA2–IB1 by the International Federation of Gynecology and Obstetrics (FIGO) 2009 in the Division of Gynecologic Oncology at Songklanagarind Hospital between January 2002 and December 2014. All pertinent clinical data from the medical records [age, ABO blood type, FIGO stage, tumor size, histology, LVSI, DSI, parametrial involvement (PI), node status, surgical margin, adjuvant therapy, and clinical outcome] were obtained and retrospectively reviewed. Information on ABO blood types was obtained from medical records or blood type identity cards. Clinical stage and histological classification were based on the criteria established by the revised FIGO 2009 and World Health Organization. Tumor size was determined by the attending gynecologic oncologist during a pelvic examination preceding surgery, and grouped into >2 cm or ≤2 cm. Tumors were classified according to cell type: squamous, adenocarcinoma, adenosquamous cell carcinoma, or other (such as small cell carcinoma or undifferentiated carcinoma). The depth of tumor invasion was
Tumor Biol. Table 2 Univariate analysis of 5year recurrence-free survival and 5-year overall survival
Variable
5-year RFS (95 % CI)
Age (year)
P value
5-year OS (95 % CI)
0.020
0.016
- 50
88.55 % (78.36–94.12)
Blood group status
94.66 % (80.82–98.60) 0.314
0.421
-O
93.13 % (85.66–96.78)
96.81 % (89.98–99.01)
-A
87.68 % (76.42–93.77)
88.22 % (67.31–96.11)
-B
81.66 % (71.23–88.60)
89.40 % (78.02–95.07)
- AB
83.12 % (43.03–96.03)
Blood group status 93.13 % (85.66–96.78)
- Non-O
83.66 % (76.27–88.91)
FIGO stage
0.145 96.81 % (89.98–99.01) 89.76 % (81.61–94.41)
0.243
- 1A2
96.15 % (75.69–99.45)
- 1B1
86.76 % (81.41–90.66)
Tumor size (cm)
0.193 100 % 92.22 % (86.89–95.44)
0.098
- ≤2
89.61 % (83.50–93.54)
- >2
82.87 % (72.60–89.56)
Histology - Squamous cell carcinoma
94.12 % (65.02–99.15) 0.154
-O
0.336 93.52 % (86.86–96.87) 91.31 % (81.97–95.93)