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Biomedical subjects

C A Szpak

Publications and source records attributed to C A Szpak.

At least 19 recordsLinked to original sources

Histologic features associated with hormonal responsiveness of ectopic endometrium.

OBJECTIVE: To correlate histologic parameters of endometriosis with hormonal responsiveness. DESIGN: Seven hundred sixty-eight unselected endometriotic implants and the corresponding intrauterine endometrium from 196 patients were classified by standard endometrial dating criteria. In addition, other histologic characteristics of endometriotic implants such as the amount of stroma, amount of fibrosis, the presence of surface epithelium, presence of focal hemorrhage, and gland characteristics were also noted. SETTING: Academic tertiary referral center. MAIN OUTCOME MEASURES: Comparison of histologic dating between endometriotic implants and the corresponding endometrium as a function of histologic parameters. RESULTS: Implants that were synchronous with the corresponding eutopic endometrium had more stroma than those that were out of phase. The amount of fibrosis was inversely related to hormonal responsiveness. The presence of surface epithelium in implants was also associated with an impaired response (28.0% versus 48.0% in phase). Endometriomas were found to be in phase with the corresponding endometrium less often than other types of implants (21.7% versus 43.3%). Although endometriomas had similar amounts of stroma when compared with other implants, they had significantly more fibrosis (850.2 microns versus 195.0 microns). CONCLUSIONS: These results suggest that the unpredictable response of endometriotic implants to cyclic endogenous hormones and hormonal therapy may be related to the architectural relationships between the cellular elements found in normal endometrium.

Endometriosis↗

Epithelial ovarian tumors of low malignant potential.

The records of 31 women with ovarian tumors of low malignant potential were retrospectively reviewed to identify factors that determine the prognosis. Median follow-up was 51 months. Eighteen women had stage I disease. Twenty-three women (74%) had serous tumors, of which 46% were bilateral. Nine patients (29%) had concomitant endometriosis or endosalpingiosis. Two patients died of disease; both had mucinous tumors with extraovarian metastases at initial operation and inadequate pathologic sampling of their tumors. These results were combined with those of 970 women identified in previous reports to show that the rate of recurrence or persistence of ovarian tumors rises from 2% for women with stage I disease to 14% for those with stage III or IV disease, while mortality rises from 2 to 5%. Careful staging and pathologic sampling are important for establishing the prognosis. Testing of adjuvant therapy should be limited to patients with extraovarian disease.

Adult↗

Computed tomography-guided fine-needle aspiration of retroperitoneal lymph nodes in gynecologic oncology.

Computed tomography-guided fine-needle aspiration was performed on 30 retroperitoneal lymph nodes in 29 patients with gynecologic cancer. There were no serious complications. Review of the cytologic material demonstrated malignant cells in 83% of the aspirates. Because the predictive value of a positive aspirate approaches 100%, therapy for metastatic disease can be initiated in these patients with the need for an open biopsy. Among five aspirates in which malignant cells were not seen, the cellularity of the specimen appeared to be the critical factor determining the predictive value of the aspirate. Whereas neither of two patients with negative aspirates of adequate cellularity has developed recurrent disease, two of three patients with hypocellular negative aspirates have. Because a hypocellular negative aspirate from a retroperitoneal lymph node may not be a true reflection of disease status, either repeat aspiration or open biopsy is advisable.

Adenocarcinoma↗

Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells.

Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.

Adenocarcinoma↗

Abdominal leiomyosarcoma: aggressive management.

We retrospectively reviewed 34 cases of intra-abdominal leiomyosarcoma treated between 1967 and 1986. Thirty-three patients had operation, and the primary tumor was removed in all but one. Fifteen patients had peritoneal implants at initial surgical exploration; 14 had tumor recurrence and had at least one reoperation. Five-year survival was 16% overall and 37% for patients without peritoneal implants at the initial procedure. This figure includes five patients in whom distant metastases developed after benign gastric or intestinal leiomyoma was diagnosed based on histologic and gross findings. All patients who have had five-year cures or more than two years of palliation after demonstration of peritoneal metastases had operation after 1978, a finding that probably reflects a more aggressive surgical approach to these tumors. Effective palliation, defined as three months of symptom relief and six-month survival in patients with widespread intraperitoneal tumor, was achieved significantly more often when the tumor causing the symptom was resected (eight of eight patients) than when it was not (five of six patients). These data indicate that an aggressive surgical approach is warranted in attempts to achieve either cure or palliation in patients with intra-abdominal leiomyosarcoma.

Actuarial Analysis↗

Uterine hemangioma associated with infertility.

An infertile woman with an enlarged uterus was thought to have leiomyoma. At laparotomy two large, vascular uterine tumors were removed; the remainder of the uterus was preserved. Evaluation of histologic sections with antibody to human factor VIII and electron microscopy were necessary to confirm the diagnosis of hemangioma.

Adult↗

The presence of stage II melanosomes (premelanosomes) in neoplasms other than melanomas.

Aside from melanomas, other nonmelanocytic pigmented tumors synthesize melanin or contain benign passenger melanocytes. While Stage IV melanosomes (mature melanosomes) occur in neoplasms which synthesize melanin as well as in those with benign companion melanocytes, Stage II melanosomes (premelanosomes), which are found in melanocytes and cells of pigmented nonmelanocytic tumors of neural crest origin, are considered the morphologic hallmark of in vivo melanin synthesis. To test this widely held concept, we studied the ultrastructure of representative malignant melanomas and other pigmented tumors (pigmented variants of the nevocellular nevus, squamous cell carcinoma, schwannoma, basal cell carcinoma, and seborrheic keratosis). Discrete intracytoplasmic Stage II melanosomes were noted in neoplastic cells of tumors of neural crest origin (melanoma, schwannoma, and nevocellular nevus), which are widely believed to synthesize melanin. In addition, they were also detected in neoplastic epithelial cells of a squamous cell carcinoma, basal cell carcinoma, and seborrheic keratosis. In these epithelial tumors, a spectrum of melanosomes from Stage II through Stage IV were presumably acquired from nonneoplastic companion melanocytes, which were an integral part of the tumor. Because squamous epithelium has not been shown to synthesize melanin, this study suggests that the finding of intracytoplasmic Stage II melanosomes does not necessarily imply melanin synthesis. When accompanied by melanocytes, epithelial and perhaps other tumors may contain ingested Stage II melanosomes.

Basal Cell Carcinoma↗

Adjunct to the diagnostic distinction between adenocarcinomas of the ovary and the colon utilizing a monoclonal antibody (COL-4) with restricted carcinoembryonic antigen reactivity.

Malignant ovarian tumors may represent either primary ovarian cancers or metastatic lesions (from patients with demonstrated primary cancers at other body sites) whose distinction may be difficult using clinical, surgical, and pathological criteria. Monoclonal antibody (MAb) COL-4, reactive with carcinoembryonic antigen, has previously been shown to react preferentially with adenocarcinomas of the colon versus a variety of normal tissues. We report here that MAb COL-4 is strongly reactive with primary colonic carcinomas (N = 50), as well as regional (N = 42), and distant (N = 20) metastases of colonic adenocarcinoma. In contrast, MAb COL-4 demonstrated little to no reactivity with primary (N = 53) and metastatic carcinomas of the ovary (N = 23) including serous, mucinous, and poorly differentiated adenocarcinomas using immunohistochemical techniques. This differential reactivity was statistically significant (P less than 0.001), suggesting the potential clinical utility of MAb COL-4 in the differentiation of ovarian from colonic adenocarcinoma. Solid-phase quantitative radioimmunoassays and Western blotting techniques confirmed these results. Data are also presented that the carcinoembryonic antigen molecules or epitopes recognized by a more classical broadly reactive anti-carcinoembryonic antigen MAb are distinct from those recognized by MAb COL-4. Other carcinomas which also metastasize to the ovary and may be confused clinically with a primary ovarian tumor such as adenocarcinomas of the stomach and breast were also evaluated for reactivity with MAb COL-4. COL-4 was also reactive with all gastric carcinomas evaluated, but failed to react with breast carcinomas. Hence, COL-4 can now be utilized as an immunohistochemical adjunct for the differentiation of ovarian from gastrointestinal adenocarcinoma which can be difficult to distinguish by clinical, surgical, and histological parameters.

Adenocarcinoma↗

Applications of immunocytochemistry to clinical cytology.

This article reviews the recent studies reporting the applications of immunocytochemistry to diagnostic problems in clinical cytology. A series of studies with monoclonal antibody (MAb) B72.3 is discussed in detail. MAb B72.3, reactive with a high molecular weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been shown previously to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from the majority of patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected tumor cells in effusion specimens from most of the patients with "non-small cell" carcinoma of the lung and with carcinoma of the ovary. MAb B72.3 was also used with fine-needle aspiration biopsies (FNABs) and corresponding surgically excised tumors to determine cellular reactivity. Positive staining with MAb B72.3 was observed in needle aspirates of the great majority of "non-small cell" carcinomas of the lung, adenocarcinomas of the breast, adenocarcinomas of the colon, and carcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, sarcomas, and glial tumors stained negatively with the antibody. Most benign lesions from the breast, lung, pancreas, parotid, and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B723. In more than 90% of these patients, the staining patterns of tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, is most selectively expressed in carcinomas, and may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in FNABs.

Animals↗

Prognostic value of peritoneal washings in patients with malignant mixed müllerian tumors of the uterus.

Peritoneal washings from 36 women with all pathologic stages of mixed müllerian tumors of the uterus (27 homologous stroma, nine heterologous stroma) were reviewed in a blinded retrospective fashion for the presence and type of malignant cells collected. Malignant tumor cells were demonstrated in the washings of 16 patients; 13 contained adenocarcinoma only, two contained adenocarcinoma and sarcoma, and one contained sarcoma cells only. Cox's logistic regression analysis showed that cytologic examination of peritoneal washings when combined with pathologic staging provides a statistically significant discriminant of disease-free survival. Patients with a favorable prognosis (pathologic Stage I and peritoneal washings free of malignancy) had sevenfold increased disease-free survival compared with survival of the patients with an unfavorable prognosis (pathologic Stages II, III, or IV or malignant cells present in peritoneal washings). Three of the 18 patients with pathologic Stage I disease manifested malignant tumor cells in the peritoneal washings and all three patients died of disease in less than 1 year. The presence of malignant cells in peritoneal washings in patients with mixed müllerian tumor apparently limited to the uterus suggests a clinical course that is similar to that of those with more advanced disease.

Adenocarcinoma↗

Use of a monoclonal antibody (B72.3) as a novel immunohistochemical adjunct for the diagnosis of carcinomas in fine needle aspiration biopsy specimens.

Monoclonal antibody B72.3 has been shown to be reactive with a high-molecular-weight glycoprotein complex termed TAG(tumor-associated glycoprotein)-72. By the avidin-biotin immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumor tissues from both malignant and benign tissues were analyzed for TAG-72 expression. Staining (range, 1 to 100 per cent of tumor cells) with monoclonal antibody B72.3 was observed in needle aspirates from 18 of 18 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, and six of six adenocarcinomas of the colon, as well as adenocarcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, and sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid, and thyroid also failed to stain. In 66 patients, tumor-bearing tissue had also been resected and was available for comparative examination with monoclonal antibody B72.3. In 62 of these 66 patients, the staining patterns in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tissues. From these studies it is concluded that monoclonal antibody B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells but not in benign cells and is most selectively expressed in adenocarcinomas. This monoclonal antibody may be used as a novel adjunct for the diagnosis of carcinoma in fine needle aspiration biopsy specimens.

Antibodies, Monoclonal↗

Phenotypic heterogeneity of a tumor-associated antigen in adenocarcinomas of the colon and their metastases as demonstrated by monoclonal antibody B72.3.

To determine the potential antigenic heterogeneity which might exist between a primary colon carcinoma lesion and its metastases, we stained the formalin and Zenker's fixed paraffin-embedded tissues from the resection specimens of 12 patients with Duke's Stage C adenocarcinoma of the colon with monoclonal antibody (MAb) B72.3. This MAb previously has been shown to react with a high molecular weight tumor-associated glycoprotein (termed TAG-72), which is selectively expressed in adenocarcinomas versus normal adult tissue. Five to 90% of malignant cells from all primary lesions stained with MAb B72.3 in paraffin-embedded tissue. A significantly diminished percentage of cells stained from the metastases in lymph nodes and distant sites. Pearson correlation coefficients showed that the antigenic expression of the metastasis in the lymph node was a better indicator of the antigenic expression of the metastasis in the distal site than was the primary lesion in the colon. These findings suggest that the effective use of monoclonal antibodies for diagnostic imaging or therapeutic purposes may require the evaluation of the antigenic expression in regional node metastases rather than that of the primary lesion.

Adenocarcinoma↗

The diagnostic distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung as defined by a monoclonal antibody (B72.3).

The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, immunohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to "carcinoembryonic antigen (CEA)" and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of human metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P greater than 0.0001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies.

Adenocarcinoma↗

Phenotypic characterization of lung cancers in fine needle aspiration biopsies using monoclonal antibody B72.3.

Monoclonal antibody B72.3, reactive with a high-molecular-weight glycoprotein tumor-associated antigen (designated TAG-72), has been previously shown to be reactive with formalin-fixed paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast and not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. In this study, fine needle aspiration biopsies of 127 lung cancers (93 primary and 34 metastatic tumors) as well as 18 benign lung lesions were analyzed with monoclonal antibody B72.3 using avidin-biotin-peroxidase techniques. Monoclonal antibody B72.3 showed reactivity with 100% of the 27 lung adenocarcinomas and adenosquamous carcinomas, with greater than or equal to 10% of tumor cells showing reactivity in 22 of 27. A lesser percentage of squamous cell carcinomas (24 of 31) and large cell carcinomas (7 of 13) were immunoreactive, and of these several were weakly reactive with less than or equal to 1% tumor cells reacting. In contrast, monoclonal antibody B72.3 failed to react with any of the 21 small cell carcinomas or one carcinoid tumor evaluated. In 35 patients tumor-bearing tissue was resected, and formalin-fixed tissue sections were also evaluated. The staining pattern and percentage of tumor cells positive in the aspiration biopsies were, in most cases, highly predictive of the reactivity observed in corresponding resected tumor. Metastatic adenocarcinomas to lung from various body sites were also immunoreactive with monoclonal antibody B72.3; however, a variety of other tumor types (including 13 melanomas) failed to stain. Staining by monoclonal antibody B72.3 was not noted in any of the 18 benign lesions aspirated, with the exception of occasional fine stippling in the cytoplasm of bronchial epithelial cells. Hence, monoclonal antibody B72.3 and fine needle aspiration biopsy techniques may be of potential use in the differential diagnosis and antigenic phenotyping of a spectrum of lung neoplasms prior to surgical resection.

Adenocarcinoma↗

Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3.

Murine monoclonal antibody B72.3, prepared against a membrane-enriched extract of human metastatic carcinoma, was reacted with a spectrum of adult and fetal human tissues using avidin-biotin-complex immunohistochemical techniques to evaluate the expression of the reactive tumor associated glycoprotein (TAG)-72 antigen. TAG-72 was shown to be expressed in several epithelial-derived cancers including 94% of colonic adenocarcinomas, 84% of invasive ductal carcinomas of the breast, 96% of non-small cell lung carcinomas, 100% of common epithelial ovarian carcinomas, as well as the majority of pancreatic, gastric, and esophageal cancers evaluated. TAG-72 expression was not observed, however, in tumors of neural, hematopoietic, or sarcomatous derivation, suggesting that the TAG-72 antigen is "pancarcinoma" in nature. Appreciable monoclonal antibody B72.3 reactivity was generally not observed in adult normal tissues, with limited reactivity noted in a few benign lesions of the breast and colon. TAG-72 antigen expression was detected, however, in fetal colon, stomach, and esophagus, thus defining TAG-72 as an oncofetal antigen. TAG-72 has previously been shown to be distinct from carcinoembryonic antigen and other tumor associated antigens. The pancarcinoma distribution and lack of significant reactivity with normal adult tissues of monoclonal antibody B72.3 suggest its potential diagnostic and therapeutic utility for human carcinomas.

Animals↗