The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease

Numata Masakatsu, Shiozawa Manabu, Watanabe Takuo, Tamagawa Hiroshi, Yamamoto Naoto, Morinaga Soichiro, Watanabe Kazuteru, Godai Teni, Oshima Takashi, Fujii Shoichi, Kunisaki Chikara, Rino Yasushi, Masuda Munetaka, Akaike Makoto

Description

The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies. Methods 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed. Results Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology. Conclusions Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

Sujets

• Colorectal cancer

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 13
• Langue: English

Extrait

Numata et al. World Journal of Surgical Oncology 2012, 10:109
http://www.wjso.com/content/10/1/109 WORLD JOURNAL OF
SURGICAL ONCOLOGY
RESEARCH Open Access
The clinicopathological features of colorectal
mucinous adenocarcinoma and a therapeutic
strategy for the disease
1* 1 1 1 1Masakatsu Numata , Manabu Shiozawa , Takuo Watanabe , Hiroshi Tamagawa , Naoto Yamamoto ,
1 2 2 2 2 2Soichiro Morinaga , Kazuteru Watanabe , Teni Godai , Takashi Oshima , Shoichi Fujii , Chikara Kunisaki ,
3 3 1Yasushi Rino , Munetaka Masuda and Makoto Akaike
Abstract
Background: The guidelines established by the National Comprehensive Cancer Network do not describe
mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies
show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we
described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic
strategies.
Methods: 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary
resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features
and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival
using Cox proportional hazard model were performed.
Results: Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a
deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate
analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous
adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II
disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in
patients with a mucinous histology.
Conclusions: Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared
with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology,
additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further
molecular investigations considering genetic features of mucinous histology will lead to drug development and
better management of peritoneal metastasis
Keywords: Mucinous adenocarcinoma, Colorectal cancer, Clinicopathological feature
* Correspondence: [e-mail]
1
Department of Gastroenterological Surgery, Kanagawa Cancer Center, 1-1-2
Nakao, Asahi-ku, Yokohama, Kanagawa 241-0815, Japan
Full list of author information is available at the end of the article
© 2012 Numata et al.; licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.Numata et al. World Journal of Surgical Oncology 2012, 10:109 Page 2 of 8
http://www.wjso.com/content/10/1/109
Background The covariates included in the study were gender, age,
Colorectal cancer is the third most common cancer and location of the tumor, size of the primary tumor, pre-
the fourth most frequent cause of cancer death world- operative serum carcinoembryonic antigen (CEA) level,
wide [1]. Mucinous adenocarcinoma (MA) is diagnosed depth of invasion, lymph node metastasis, distant metas-
when more than 50% of the tumor comprises a mucin- tasis, operating facility, and histological type. The patho-
ous pattern upon histological examination [2]. MA logical tumor status was coded using the TNM
makes up 6 to 20% of all colorectal cancers [3-8], and classification system [24]. The use of adjuvant chemo-
differs from non-mucinous adenocarcinoma (NMA) therapy for patients with curative resection, as well as
with regard to its clinicopathological characteristics, dis- additional therapy (chemotherapy and/or surgery) for re-
tinct genetic profiles, and pathogenic pathways [9-12]. current and non-curative cases were also recorded.
The prognostic significance of MA is controversial. In In the analysis of the survival rates, all cases were
previous studies, mucinous histology was reported not divided into 3 groups, that is, patients without any me-
to be an independent prognostic factor for survival tastases (stage 0 to II [24]), patients with regional lymph
[13,14]. The guidelines established by the National Com- node metastasis but without distant metastasis (stage
prehensive Cancer Network (NCCN) do not describe III), and patients with distant metastasis (stage IV).
mucinous histology as a clinical factor that should influ-
ence the therapeutic algorithm [15,16]. However, in Statistical analysis
some studies, it is reported that MA is associated with The two groups of patients (MA and NMA) were com-
2
worse clinicopathological characteristics [17-19] and a pared using 2×2 tables for binary factors using the χ -
poorer prognosis than NMA [5,17,20-23]. test, or Fisher’s exact test where appropriate. Overall
The lack of a consensus may be the result of the low survival was calculated from the date of surgery for the
ratio of MA to all colorectal cancers and the limited de- primary lesion until death from any cause, or was cen-
tection power to clarify the differences between MA and sored at the last follow-up visit. Survival data were ana-
NMA. lyzed using the Kaplan-Meier method. A comparison of
We conducted a retrospective analysis of patients with survival curves was carried out using the log-rank test.
colorectal cancer at two major centers to identify the The prognostic significance was analyzed by multivariate
clinicopathological features of MA, and also investigated Cox proportional hazard models. P-values<0.05 were
the recurrence to establish an optimal therapeutic strat- considered statistically significant, and all P-values cor-
egy for MA. respond to two-sided significance tests.
Results
Methods Of the 2,817 colorectal cancer patients, MA accounted
Patients for 5.1% (144) of the colorectal cancer cases. The distri-
The data from 2,817 patients with colorectal cancer in bution of the patients’characteristics is shown in Table 1.
two major centers, Kanagawa Cancer Center and Yoko- The distribution for gender, age, and location of MA
hama City University Medical Center, between 2001 and was similar to that of NMA. The patients with MA had
2010 were investigated. Written informed consent was significantly larger primary lesions, higher preoperative
obtained from the patient for publication of this report serum CEA levels, deeper invasion, higher nodal and
and any accompanying images. All patients initially distant metastasis rates, and a larger number of meta-
underwent resection of a primary lesion followed by ad- static sites compared to the patients with NMA.
juvant chemotherapy when diagnosed as stage III dis- Table 2 shows the distribution of treatment factors, in-
ease. In tumor, node metastases (TNM) stage T3 to T4, cluding the curability of the first surgery, rate of adju-
lower-rectal cases, total mesorectal excision (TME) and vant chemotherapy, chemotherapy for advanced or
lateral node dissection were routinely performed at ini- recurrent cases, and additional surgery for liver and lung
tial resection. No patients were treated with neo- or ad- metastasis. For these factors, there were no significant
juvant radiation therapy. differences between the MA and NMA groups. Unlike
The analyzed patients were diagnosed with MA, western countries, neo- or adjuvant radiation therapy for
defined as tumors with more than 50% of the tumor vol- patients with stage II and III disease is not commonly
ume comprising mucin, or with NMA, defined as performed in Japan.
tumors without any mucinous features, or with a less To clarify the prognostic factors for colorectal cancer,
than 50% mucinous component [2]. Patients diagnosed univariate and multivariate analysis were carried out. Mu-
with signet ring cell carcinoma, undifferentiated carcin- cinous histology was noted to be one of the independent
oma, and other histological types were excluded from prognostic factors for overall survival in univariate and
the analysis. multivariate analysis (Tables 3 and 4). The 5-year relativeNumata et al. World Journal of Surgical Oncology 2012, 10:109 Page 3 of 8
http://www.wjso.com/content/10/1/109
Table 1 Comparison of clinicopathological characteristics Table 2 Comparison of treatment factors in
in non-mucinous and mucinous adenocarcinoma non-mucinous and mucinous adenocarcinoma
Characteristics NMA MA P-value Treatment factors NMA MA P-value
(n=2,673) (n=144) Curability of first surgery n=2,673 n=144 0.063
Gender 0.772 Complete 2,411 123
Female 1,072 56 Incomplete 262 21
Male 1,601 88 Curability of first n=1,157 n=57 0.885
surgery in rectal cancer
Age, years 0.271
Complete 1,101 54
< 65 1,183 57
Incomplete 56 3
≧ 65 1,490 87
Lateral node n=1157 n=57 0.104
Location 0.090
dissection in rectal cancer
Colon 1,516 92
Yes 189 14
Rectum 1,157 57
No 968 43
Size, cm < 0.001