Mehrdad Nadji

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.

Receptors Reconsidered: A 20-Year Perspective

Publisher Summary The original discovery of steroid hormone receptors and essentially all information concerning their interaction and function in target cells have depended on experiments in which a radioactive steroid serves as a marker for the receptor protein to which it binds. The female reproductive tissues, such as uterus, vagina, and anterior pituitary, contain a characteristic estrogen-binding component which was first indicated by their striking ability to take up and retain tritiated hexestrol and estradiol after the administration of physiological doses of these substances to immature animals. This chapter discusses the biochemical mechanism by which the reaction of estradiol and other estrogenic hormones with receptor substances elicits hormonal response has been the subject of extensive investigation. The activated steroid-receptor complex is translocated to the nucleus where it binds to chromatin and in some way modulates RNA synthesis which appears to be characteristically restricted in hormone-dependent tissues.

A Tissue Fixative that Protects Macromolecules (DNA, RNA, and Protein) and Histomorphology in Clinical Samples

Preservation of macromolecules (DNA, RNA, and proteins) in tissue is traditionally achieved by immediate freezing of the sample. Although isolation of PCR-able RNA has been reported from formalin-fixed, paraffin-embedded tissues, the process has not been shown to be reproducible because high molecular weight RNA is usually degraded. We investigated the potential value of a new universal molecular fixative (UMFIX, Sakura Finetek USA, Inc., Torrance, California) in preservation of macromolecules in paraffin-embedded tissue. Mouse and human tissues were fixed in UMFIX from 1 hour to 8 weeks. They were then processed by a rapid tissue processing (RTP) system, embedded in paraffin, and evaluated for routine histology as well as for the quality and quantity of DNA, RNA, and proteins. Formalin-fixed tissues were processed by RTP and evaluated in a similar manner. Fresh-frozen samples were used as controls. The morphology of UMFIX-exposed tissue was comparable to that fixed in formalin. High molecular weight RNA was preserved in tissue that was immediately fixed in UMFIX and stored from 1 hour to 8 weeks at room temperature. There were no significant differences between UMFIX-exposed and frozen tissues on PCR, RT-PCR, real-time PCR, and expression microarrays. Similarly, physical and antigenic preservation of proteins in UMFIX tissue was similar to fresh state. Both RNA and proteins were substantially degraded in formalin-fixed and similarly processed specimens. We concluded that it is now possible to preserve histomorphology and intact macromolecules in the same archival paraffin-embedded tissue through the use of a novel fixative and a rapid processing system.

Surgically defined prognostic parameters in patients with early cervical carcinoma: A multivariate survival tree analysis

This study was performed to identify a statistical combination of independent pathologic and clinical features that best predict 5‐year disease free survival (DFS) in patients with early stage cervical carcinoma treated by radical hysterectomy. The main goal of the study was to identify subsets of patients based on risk factors with maximal differences in DFS.

Analysis of thyroid transcription factor-1 and cytokeratin 20 separates merkel cell carcinoma from small cell carcinoma of lung

Merkel cell carcinoma needs to be separated from small cell carcinoma metastatic from visceral sites to skin. Pulmonary small cell carcinoma is the most common primary site of small cell carcinoma. We evaluated the immunophenotypic characteristics of 21 Merkel cell carcinomas and 33 small cell carcinomas of lung using thyroid transcription factor‐1 and cytokeratin 20. Thyroid transcription factor‐1 was 100% specific for the diagnosis of small cell carcinoma of lung associated with a diagnostic sensitivity of 85%. Cytokeratin 20 was present in 95% of Merkel cell carcinomas; however, 33% of small cell carcinoma of lung were also positive. Both antibodies typically demonstrate diffuse and intense staining of their respective tumor cells. We conclude that thyroid transcription factor‐1 is a sensitive and specific marker for small cell carcinomas of lung and that a combination of thyroid transcription factor‐1 and cytokeratin 20 is indicated to assist in the differentiation of metastatic small cell carcinoma of lung from merkel cell carcinoma.

Microinvasive carcinoma of the cervix

Background. Microinvasive carcinoma of the cervix (MIC) has been poorly defined in the past and is still a focus of persistent controversy. In 1985, the International Federation of Gynecology and Obstetrics (FIGO) defined Stage IA as “preclinical invasive carcinoma, diagnosed by microscopy only,” subdividing it into Stage IA1 or “minimal microscopic stromal invasion,” and Stage IA2 or “tumor with invasive component 5 mm or less in depth taken from the base of the epithelium and 7 mm or less in horizontal spread.” In 1974, the Society of Gynecologic Oncologists (SGO) defined MIC as any lesion with a depth of invasion of 3 mm or less from the base of the epithelium, without lymphatic or vascular space invasion.

Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans

Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimers disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E‐deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (‐80%), HDL/TC, and HDL/LDL ratios (‐93% and ‐96%, respectively), esterification rate in apo B‐depleted plasma (+ 100%), plasma triglyceride (+200%), hepatic HMG‐CoA reductase activity (‐50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37‐wk‐old male apo E‐KO mice. Apo E‐KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogene‐sis without affecting lipase activities, endogenous anti‐oxidant capacity, or appearance of neurodegenerative markers in 37‐wk‐old male mice.—Moghadasian M. H., McManus B. M., Nguyen, L. B., Shefer, S., Nadji M., Godin D. V., Green, T. J., Hill, J., Yang, Y., Scud‐amore C. H., Frohlich J. J. Pathophysiology of apoli‐poprotein E deficiency in mice: relevance to apo E‐related disorders in humans. FASEB J. 15, 2623–2630 (2001)

Prognostic Factors of Early Stage Cervical Cancer Treated by Radical Hysterectomy

Background. This study was performed to identify pathologic and clinical features that best correlate with lymph node metastasis and disease free survival among patients with Stage I and II cervical cancer treated by radical hysterectomy.

C-cell hyperplasia in thyroid tissue adjacent to follicular cell tumors

An immunohistochemical study was conducted on the number and distribution of C-cells in the nonneoplastic thyroid tissue adjacent to tumors of follicular cell origin. It consisted of 49 cases, of which 25 were papillary carcinomas, 22 were follicular adenomas, and 2 were follicular carcinomas. Twenty normal adult thyroids from the Browards Medical Examiners morgue served as controls. In 17 of the 49 cases (34.6%), there was a statistically significant increase in the number of C-cells in the normal-appearing thyroid tissue adjacent to follicular cell tumors, with at least 50 C-cells in one low power field, while only one of 20 normal thyroids had a similar number of cells. (P = .02; chi 2 = 5.05). In two tumor cases there were more than 100 C-cells in several low power fields with formation of small C-cell nodules similar to those described in the type II Multiple Endocrine Neoplasia Syndrome (MEN). It was concluded that the nonneoplastic thyroid tissue adjacent to 34.6% of tumors with follicular cell phenotypes contains significantly more C-cells than those present in normal adult thyroids. The possible pathogenesis and clinical significance of these findings are discussed.

Carcinoembryonic antigen present in human eccrine sweat

Carcinoembryonic antigen is detectable by standard unlabeled peroxidase-antiperoxidase technics in eccrine and apocrine secretory and ductal cells. Carcinoembryonic antigen is also present in the cuticle which lines the duct. In eccrine sweat, carcinoembryonic antigen activities were at least thirty times that in serum, using a radioimmunoassay. Carcinoembryonic antigen may form part of the Schiff-positive cuticle and function in the normal homeostasis of eccrine and apocrine glands.