Azorides R. Morales

Prostatic‐specific antigen: An immunohistologic marker for prostatic neoplasms

Antiserum to a human prostate‐specific antigen was raised in a rabbit and utilized by immunoperoxidase staining to evaluate its potential value as a diagnostic histologic marker for tumors of prostatic origin. All primary and metastatic prostatic malignancies reacted positively, whereas nonprostatic neoplasms did not stain with this procedure. This is the first immununohistochemical marker for prostate gland epithelium which does not represent prostatic acid phosphatase.

Histologic markers in primary and metastatic tumors of the liver.

To investigate the value of different tissue markers in the histologic diagnosis of hepatic tumors, we performed immunoperoxidase stains for alpha‐fetoprotein (AFP), alpha‐1‐antitrypsin (AAT), carcinoem‐bryonic antigen (CEA), and an erythropoiesis‐associated antigen (ERY‐1) on formalin‐fixed, paraffin‐embedded samples from 107 primary and metastatic tumors of the liver. AFP was present in 17% of the hepatocellular carcinomas, in 7% of the metastatic carcinomas, and in none of the cholangiocarcinomas. AAT was present in 41% of the hepatocellular carcinomas, in 37% of the cholangiocarcinomas, and in 50% to 70% of the metastatic carcinomas of the liver. Intracytoplasmic CEA was found in 75% of the cholangiocarcinomas, in 92% to 100% of the metastatic carcinomas, and in only one of the mixed hepatocellular‐cholangiocarcinomas. ERY‐1 was present in 89% of the hepatocellular carcinomas, whereas none of the cholangiocarcinomas or metastatic carcinomas stained for this marker. We conclude that immunohistochemical assays for AFP and AAT are of limited value in the differential diagnosis of hepatic tumors. However, immunohistochemical stains for ERY‐1 and CEA can be valuable in differentiating hepatocellular carcinomas from metastatic tumors.

Experience With an Automated Microwave-Assisted Rapid Tissue Processing Method

We studied the effect of a fully automated microwave-assisted rapid tissue processor (RTP) on histologic examination and on the turnaround time for surgical pathology reports. A quality assurance program reviewed the histologic sections obtained by the rapid processing method for the last 3 calendar years. In addition, the histologic results from this method were compared blindly with those obtained from the conventional overnight tissue processing (CTP) method by 9 pathologists with different levels of experience. The surgical pathology turnaround times for 1 year of use of the RTP were compared with the last year for CTP. We found that the RTP reproducibly yielded histologic material comparable in quality to CTP. The turnaround time for surgical pathology reports was improved substantially, and, in particular, same-day reporting was achieved in approximately 55% of cases compared with fewer than 1% before use of the RTP. Moreover, use of the RTP enhanced safety by eliminating formalin and xylene from the procedure.

Cathepsin D in host stromal cells, but not in tumor cells, is associated with aggressive behavior in node-negative breast cancer

One hundred fifty-four axillary lymph node-negative invasive ductal carcinomas of the breast were immunohistochemically evaluated for the expression of cathepsin D. Formalin-fixed paraffin sections of each tumor were stained using a polyclonal antibody raised against recombinant procathepsin D. Cathepsin D content of tumor cells and host histiocytes and fibroblasts within or immediately at the invasive border of tumors were assessed separately and correlated with histomorphology, estrogen-receptor content, and patients survival data. Positive cathepsin D staining of tumor cells was associated with a lower nuclear grade and well-differentiated histology, whereas moderate to strong staining of host cells correlated with larger tumor size, higher nuclear grade, poorly differentiated histomorphology, and lack of estrogen-receptor (ER) protein. No statistically significant correlation was found between cathepsin D in tumor cells and survival. There was, however, a statistically significant correlation between moderate to strong cathepsin D staining of host cells and shorter disease-free and overall survivals. Expression of cathepsin D by host cells, however, did not have an independent influence on survival. The authors conclude that cathepsin D in stromal cells, but not in tumor cells, is associated with aggressive behavior in node-negative invasive ductal carcinomas of breast. Furthermore, determination of cathepsin D in cytosolic extracts of tumors is of no practical value because it may represent cathepsin D content of tumor cells, intratumoral host cells, or both.

Her2 Expression in Prostatic Cancer: A Comparison With Mammary Carcinoma

PURPOSEnThere is growing interest in HER2 and its downstream signaling pathway molecules as treatment targets in human malignancies, including prostatic carcinoma. We used a standard Food and Drug Administration approved HER2 immunohistochemical kit to study HER2 expression in prostate cancer. We compared the results with those reported for mammary carcinoma.nnnMATERIALS AND METHODSnFor this study we selected 216 specimens obtained from patients who underwent radical prostatectomy for primary untreated prostatic carcinoma. Immunohistochemical staining was performed using the HercepTest kit (Dako Corp., Carpinteria, California) in strict fashion according to the technical and analytical protocols outlined in the kit.nnnRESULTSnOf the tumors 33 (15%) were positive for HER2, including 31 (94%) that were only weakly positive (2+). Of the HER2 positive tumors 97% were Gleason grade 7 or higher. Of the 33 positive cases 22 (67%) showed only a focal positive reaction for HER2 in discrete tumor areas.nnnCONCLUSIONSnHER2 is expressed in a minority of untreated primary prostatic carcinomas. Unlike in mammary carcinoma, HER2 positivity in prostatic cancer is usually weak in intensity and focal in distribution. While the former casts doubt on the usefulness of HER2 as a potential treatment target for most primary untreated prostatic cancer, the latter phenomenon may lead to false-negative results if the test is performed in small biopsies. Furthermore, HER2 staining of prostatic carcinoma can be technically and analytically reproducible provided that there is strict adherence to the outlined methodologies and interpretation.

Carcinoembryonic antigen in normal, preneoplastic and neoplastic gallbladder epithelium

Carcinoembryonic antigen (CEA) was found in normal epithelium, premalignant lesions, and all histologic types of carcinomas of the gallbladder. Immunocytochemical staining for CEA was limited to the apical surface of normal epithelium. In premalignant lesions and in carcinomas, the staining was more extensive, occurring within the cytoplasm and gland secretions. These findings show that the presence and the pattern of distribution of CEA in normal and neoplastic gallbladder epithelium closely resemble that in other gastrointestinal epithelia.

IMMUNOHISTOCHEMISTRY OF PROSTATIC ACID PHOSPHATASE

Acid phosphatases, a heterogeneous group of enzymes present in a variety of normal and abnormal tissues, have been in use as an aid in the diagnosis of prostatic carcinomas since the original description by Gutman and coworkers. In parallel to serum enzymatic studies, histochemical stains for acid phosphatase have also been employed in the morphologic evaluation of presumed carcinomas of the pr~state..~ These stains, however, did not gain wide acceptance because of the requirement for frozen formalin-fixed or fresh tissue, a serious drawback, since usually the question of the possible prostatic origin of a neoplasm is raised only after the evaluation of paraffin-embedded material. Furthermore, and in common with biochemical assays of yesteryear, the lack of organ specificity limited the clinical value of these stains. In recent years, it has been shown that prostatic specific acid phosphatase (PSAP) is immunologically distinct from acid phosphatases of other sources and consequently specific antibodies to PSAP have been produced and well characte r i~ed .~-* With the availability of these antibodies, immunohistochemical investigation of PSAP in neoplastic and nonneoplastic prostatic epithelium is now possible. Indirect immunofluorescence methods utilizing antibodies direc:ted against PSAP of sperm-free ejaculates have detected neoplastic prostatic epithelium at the primary or metastatic sites6. Immunofluorescence techniques, however, require fresh-frozen tissue and, in addition to the requirements for fluorescent microscopy, present a number of disadvantages similar to those of enzyme histochemistry. These difficulties are obviated with immunoperoxidase techniques whose only limitation, in common with immunofluorescence, is a requirement for highly specific antibodies. It is not surprising, therefore, to observe a rapid proliferation of reports describing the diagnostic value of immunoperoxidase procedures for PSAP in the histogenetic assessment of primary and metastatic prostatic turn or^.^^^ The details of technical aspects of immunopernxidase staining for PSAP have been published previ~usly. ~