Gallbladder carcinomas

Gallbladder carcinomas: An immunoprognostic evaluation of P53, Bcl-2, CEA and alpha-fetoprotein

Cancer of the gallbladder is the fifth most common can­cer of the digestive tract. The mean five-year survival rate has remained at 1% despite surgical intervention; this is mainly attributed to its late presentation, with extensive lo­cal spread and concomitant invasion of the liver. It is now accepted that most cases of invasive gallbladder cancers arise from precursor lesions of intestinal metaplasia, dysplasia and carcinoma in situ lesions. The adenoma-cancer sequence is recognized in the minority of cases. In this study, the expres­sion of P53, Bcl-2, carcinoembryonic antigen (CEA) and alpha-fetoprotein was evaluated in both the in situ and inva­sive components of the tumour, and the results were corre­lated with their mean survival.

MATERIALS AND METHODS

One hundred clinical cases of documented gallbladder carci­nomas were reviewed. Twenty-eight de novo carcinomas were randomly selected for the study (Figures 1A,B). All clinical details regarding outcomes were obtained from their chart reviews. The mean survival intervals were assessed for each case. Tissue blocks pertaining to these cases were ob­tained from the files of the Department of Pathology, Royal University Hospital, Saskatoon, Saskatchewan. All of the tissue had been fixed in 10% buffered formalin and embed­ded in paraffin. Five micron-thick sections were stained with hematoxylin-eosin and assessed by two pathologists inde­pendently. Representative blocks were selected for immuno- histochemistry. This was performed using a standard strepa- vidin-biotin method after antigen retrieval. The antibodies used, their source and their dilutions are listed in Table 1.

TABLE 1 Antibodies used

Antibody

Type

Dilution

Source

P53 (DO7)

Mouse

1/50

DAKO(M7001)

Carcinoembryonic antigen

Rabbit

1/5000

DAKO(AO115)

Alpha-fetoprotein

Rabbit

1/6000

DAKO(A0008)

Bcl-2

Mouse

1/100

DAKO(M0887)

 

Figure 1) A Hematoxylin and eosin staining

Figure 1) A Hematoxylin and eosin staining demonstrating the carcinoma in situ component in the gallbladder. Marked cytological atypia limited to the epithelial cells of the mocosa is apparent. B Hematoxylin and eosin staining elucidating the invasive component of gallbladder carcinoma. Marked architectural distortion with invasive malignant glands are clearly identified

In each case, the entire section was systematically exam­ined for immunoreactivity to the various antibodies in both the in situ and invasive components of the tumour. Only im- munoreactive nuclear-stained cells were recorded as being P53 positive (Figures 2A,B). By using a combination of the percentage of positive cells and their intensity of staining, the stained sections were assessed as negative, weak (+), moderate (++) and strong (+++) by semiquantitative analy­sis. The staining patterns of the in situ and the invasive com­ponents were correlated to their mean survival.
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Figure 2) A P53 staining of the carcinoma

Figure 2) A P53 staining of the carcinoma in situ component is strong and intranuclear. B P53 positive immunoreactivity of the invasive component is also strong and intranuclear

Category: Cancer / Tags: Alpha-fetoprotein, Bcl-2, Carcinoembryonic antigen, Gallbladder carcinoma, P53

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