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Turkish Journal of Cancer
2008, Volume 38, Number 3, Page(s) 118-122
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Colorectal carcinomas: Clinicopathologic investigation, correlation with expression of estrogen and progesterone receptors
TULU EMRE EKEM1, BURAK BAHADIR2, BANU DOĞAN GÜN2, SİBEL BEKTAŞ2, GÜRKAN KERTİŞ2, GAMZE YURDAKAN2, ŞÜKRÜ OĞUZ ÖZDAMAR2
1Zonguldak Atatürk State Hospital, Department of Pathology, Zonguldak-Turkey
2Zonguldak Karaelmas University Faculty of Medicine, Department of Pathology, Zonguldak-Turkey
Keywords: Colorectal adenocarcinoma, estrogen receptor, progesterone receptor
Summary
Correlation in mortality data between breast cancer and colonic cancer, and increased incidence of colonic cancer in women with breast cancer suggest common factors in their etiology. Similarly protective effect of increasing parity from colonic cancer, and relatively better prognosis in women may imply a common role for sex steroid hormones. In this study clinicopathologic parameters as well as estrogen and progesterone receptor expressions of 60 cases of colorectal adenocarcinoma were investigated. Most carcinomas were moderately differentiated; stage B2 tumors were predominately located in the rectosigmoid area. Immunohistochemically, no nuclear staining was demonstrated for estrogen or progesterone receptors; only six displayed cytoplasmic staining with estrogen receptor. Although potential importance of estrogen and progesterone receptors has been emphasized by certain reports, its importance is still controversial in terms of both prognosis and management. Moreover, it is unclear whether to exclude cytoplasmic staining. The significance of these receptors in colorectal carcinoma needs to be further studied. [Turk J Cancer 2008;38(3):118-122]
  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Introduction
    Colorectal adenocarcinoma is the fourth most frequently diagnosed visceral and the second leading cause of cancer mortality in both genders[1]. The correlation in mortality data between breast cancer and colonic cancer, and the increased incidence of colonic cancer in individual women with breast cancer suggest common factors in their etiology[2,3]. The protective effect of increasing parity from colonic cancer, similar to breast cancer and relatively better prognosis in women may also imply a common role for sex steroid hormones[4-8]. The potential importance of estrogen and progesterone receptors is emphasized by evidence of protection by hormone replacement therapy in women and, by a suggestion that the anti-estrogen tamoxifen may enhance the risk of colorectal cancer[9,10].
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  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Material and Methods
    In this study, clinicopathologic parameters of 60 colorectal adenocarcinomas diagnosed in the Department of Pathology in Zonguldak Karaelmas University Faculty of Medicine from November 2001 to March 2006 were retrospectively evaluated in terms of age, gender, pathological diagnosis including tumor location, lymph node status, and perineural and lymphovascular invasion. Using infiltrative ductal carcinoma of breast as control estrogen and progesterone receptor expressions were investigated immunohistochemically; nuclear staining more than 5% of tumor cells were accepted positive.
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  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Results
    Thirty-one cases were men and 29 were women with an age distribution ranging from 33 to 90 (average 65.8; SD: ± 13.55). Two cases were younger than 40 years.

    Eighteen of the sixty cases were from rectosigmoid, followed by 13 from rectum, 6 from sigmoid, each 5 from ascending colon and descending colon, 4 from transverse colon, and 3 from cecum (Figure 1). 6 cases comprised more than one segment; 4 involving ascending and transverse colon and 2 cecum, ascending and descending colon.

    Fig 1: Locations of colonic adenocar cinomas

    Histologic grading for well, moderately and poorly differentiated tumors were consecutively found 17 (28.3%), 37 (61.7%) and 6 (10.0%). Most cases were classified either in B2 (28 cases; 47%) or C2 (21 cases; 35%) according to the Astler Coller staging; stages B1 (5 cases; 8%) and D (6 cases; 10%) constituted the remainder. The correlation of histologic grade with Astler Coller stages is provided in table 1.

    Table 1: Correlation between histologic grade and Astler Coller stage

    There were vascular and perineural invasion in 23 cases and lymph node metastasis in 24 cases (Figure 2). The correlation of lymph node metastasis with tumor grade is given in table 2.

    Fig 2: Lymph node metastasis, and vascular and perineural invasion (%)

    Table 2: Correlation of lymph node metastasis and histologic grade

    Immunohistochemically no nuclear staining was demonstrated by estrogen or progesterone receptors with exception of six cases displaying cytoplasmic reaction for estrogen receptor (Figure 3).

    Fig 3: Cytoplasmic estrogen receptor staining in colorectal adenocarcinoma (x200)

  • Top
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Discussion
    Colorectal adenocarcinoma primarily affects elderly people; increases by the sixth decade and reaches its peak incidence between 60 and 70 years; mean age for both gender is about 62-63[4,8,11-13]. Its incidence under 50 years reaches up to 20% as much and unless there is an underlying condition with predisposition to colorectal carcinoma, it is exceptionally rare under 40 years[13]. Correspondingly, this study revealed similar findings, almost akin to the given data.

    Although proximal tumors seem to be increased during the last few decades, approximately 50% of all carcinomas occur in the rectosigmoid area as noted in the current study[4,11,14]. However, tumors in cecum and ascending colon were fairly less than expected. Likewise, the proportion of well-differentiated tumors was remarkably higher (28%) than poorly differentiated tumors (10%) on the contrary to general observation in which almost the same incidence for both grades (about 15% to 20%) is shared[12]. Indubitably, stage is the most important determinant in predicting the prognosis; and notably localized (i.e. stage A) tumors seem to have a tendency to increase compared to the decline in tumors with advanced stages[13,15]. Unfortunately, in our series there was no stage A tumor and stage B1 tumors were relatively low. Consequently, tumors with advanced stages (and probably with poor prognosis) constituted the majority; more than half were stage B2. Another controversial and interesting finding was the absence of lymph node metastasis in six poorly differentiated tumors, which may partially be explained by inadequate lymph node excision due to surgical procedure or specimen handling.

    Hormonal basis of colon cancer has also been a matter of consideration besides genetic predisposition and potential role of steroid hormones in both carcinogenesis and tumor progression has been indicated[16,17]. When equivalent age groups are regarded colon cancer is relatively less frequent in females[4,5]. Nullipara women has a greater risk than multipara suggesting the protective effect of increasing parity and hormone replacement therapy is supposed to reduce development of colon cancer[6-11,18]. Moreover, coexistence of colon cancer and breast cancer is relatively high[2,3]. Expressions of ER and PR have been shown in several extramammary malignant neoplasms including esophagus, stomach, lung, pancreas and gallbladder[3,16,19-26]. ER expression in malignant cells of gastric mucosa was proposed to be an independent negative prognostic factor[21]; tamoxifen therapy was found to be associated with prolonged survival[19].

    Comparable studies, either biochemically or immunohistochemically, revealed that both normal and malignant colonic mucosal cells may express ER and/or PR[9,24,27-37]. By biochemical methods, ER exhibited a wide range, varying about 20% to 54% and while PR expression was about 42%[9,24,31,34-39]. In addition, ER and PR levels in colonic cancers are usually lower than in mammary cancers and thus it may be difficult to detect immunohistochemical expression in gastrointestinal cancers with lower levels[31,36,40]. The absence of nuclear staining for both receptors in the current study may also be explained by low levels of receptors probably causing immunohistochemically undetectable expression. In the largest immunohistochemical study composed of 156 colon carcinomas, none was positive for ER, and only one case was reactive for PR while surrounding nontumoral mucosa was stained with both receptors[9]. On the other hand, ER and PR reactions were consecutively found 32% and 23% by Kaklamanos et al.[34]. There are also some conflicting reports regarding ER and PR status[32,35,36]. In terms of immunohistochemical staining pattern nuclear staining of more than 5% of tumor cells are generally accepted positive while cytoplasmic reaction is considered non-specific. However, some reports proposed that cytoplasmic ER staining should be considered[9]. No nuclear reaction for ER or PR was observed in this study; six cases demonstrated cytoplasmic ER. In part, this may be attributed to low receptor levels as previously stated. It may also be associated with other causes such as cell characteristics affected by tissue processing, immunohistochemical method, and perhaps clonality of antibodies[9,35].

    The potential importance of estrogen and progesterone receptors is emphasized by evidence of protection by hormone replacement therapy in women and, by a suggestion that the anti-estrogen tamoxifen may enhance the risk of colorectal cancer[9,10]. Patients with ER expression are suggested to have a better survival rate[9,39]. This observation was supported by animal models and anti-estrogenic therapy was experimentally proved to reduce the incidence of colon cancer[41,42]. Nevertheless, patients receiving tamoxifen therapy for breast cancer have a relative risk for colorectal carcinoma[17]. Moreover, mechanisms other than receptor status may contribute to positive tamoxifen effect in colorectal cancers[22]. Therefore, as well as their detection, significance of ER and PR receptors is still controversial in terms of both management and prognosis.

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  • Introduction
  • Methods
  • Results
  • Discussion
  • References
  • References

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  • Top
  • Introduction
  • Methods
  • Results
  • Discussion
  • References
  • [ Top ] [ Summary ] [ PDF ] [ Similar Articles ] [ Mail to Editor ]
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