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F E Sharkey

Publications and source records attributed to F E Sharkey.

At least 37 records · Page 2Linked to original sources
PubMed1985

Observer reproducibility during computer-assisted planimetric measurements of nuclear features.

To evaluate observer variance during microprocessor-assisted planimetry, nuclear features (area, perimeter, and form factor) were studied in a series of mammary ductal carcinomas. Fragments of formalin-fixed, paraffin-embedded tissue were re-embedded in plastic, sectioned at 1 micron, stained with methylene blue, and studied with a Zeiss-Kontron MOP-3 microprocessor-assisted planimeter. Both interobserver and intraobserver reproducibility were evaluated, the former among three different observers and the latter by two observers repeating their own measurements. Reproducibility was good for measurement of area, but deteriorated progressively for measurement of perimeter and form factor. Not only was observer correlation poor (identified via linear regression), but paired t-tests also showed consistent variation among observers. The major difficulty was in following the irregular nuclear contours that are characteristic of cancer cells. It is concluded that adequate demonstration of observer reproducibility remains an essential part of tissue investigation, even when the objective methods typical of morphometry are used.

Breast Neoplasms↗
PubMed1985

Changes in histological differentiation of human tumors transplanted to athymic nude mice: a morphometric study.

Differing conclusions have been reached regarding the phenotypic stability of human tumors transplanted to athymic nude mice. Since previous conflicting studies of tumor histology have been largely subjective, quantitative methodology was applied to an analysis of 13 human adenocarcinoma tumor lines that were originally derived directly from surgical specimens. Glandular differentiation was quantitated, both in the original human tumor (OHT) and in a minimum of 6 serial passages of the nude mouse-grown tumors (MGT), by means of point counting. A significant change in differentiation was noted in 12 lines, with 9 showing a decrease. Variance from the OHT was most commonly noted in the initial MGT, but additional changes were also noted in 8 lines during subsequent passages. Most of the lines also showed increased necrosis in the MGTs. Since histological differentiation and necrosis are related to tumor aggressiveness, it would appear that the predominant tendency was to evolve toward a more malignant phenotype. These changes may mimic those seen in human tumor metastases.

Adenocarcinoma↗
PubMed1985

Morphologic identity of primary tumor and axillary metastases in breast carcinoma. A quantitative study.

The amount of glandular differentiation was quantitated in 64 cases of primary human mammary ductal carcinoma (PR) and their axillary lymph node metastases (LNMs) to identify differences between the two groups and their effect on patient prognosis. A significant difference between a PR and any of its LNMs was uncommon (less than 5% of the cases), and variation between each PR and its LNMs was directly proportional to the amount of differentiation within the PR itself. Variance among the LNMs was proportional to that found within the PR. Each LNM usually varied as much within itself as it did from the other LNMs. Prognosis was not affected by the LNMs being less differentiated than the PR, nor vice versa. This study has provided no evidence for selection of a morphologically more aggressive tumor clone during this phase of the metastatic process, but selection by other morphologic or functional parameters is not excluded.

Axilla↗
PubMed1984

Considerations in the use of nude mice for cancer research.

Transplants of human tumors in nude mice have shown a progressive increase during the past 15 years as an experimental model for cancer research. A variety of factors, including relatively fragile health, have been identified that require appropriate experimental controls if the investigator is obtain consistent results. Not all tumors grow in nude mice. The frequency of tumor 'take' varies according to tumor origin, tumor type, inoculation site, age and conditioning of the mouse host, and a variety of other factors. Manipulation of these variables has led to successful propagation of almost every known variety of human malignancy. Following transplant, changes in characteristics have been documented, but the frequency and degree of such changes remains uncertain. Tumor growth rate probably increases after transplantation, requiring great care in the interpretation of chemotherapy experiments, but biochemical characteristics may be more stable. The nude mouse offers great interest as a model for the in vivo study of metastasis, as a number of experimental variables, mainly immunological, have been shown to affect this process. Spontaneous tumors have been shown to arise in these animals, but the controversy over their frequency relative to the thymus-bearing background strain is unresolved. We conclude that the nude mouse/tumor xenograft model, while requiring meticulous experimental controls, is nevertheless an extremely useful tool for cancer research.

Animal Husbandry↗
PubMed1984

Correlation between stage and grade in prostatic adenocarcinoma: a morphometric study.

The independence of stage and grade as prognostic factors for prostatic carcinoma is unclear. Previous studies have been hampered by both the uncertain reproducibility of subjective grading systems and the lack of a scalar grading measure, and have reached opposing conclusions. To examine this question, we quantitated via point-counting the per cent of tumor cells showing glandular differentiation in 90 cases of primary prostatic adenocarcinoma. Patient records were examined retrospectively to verify both the stage at presentation and follow-up. Stage and morphometric grade were found to be inversely correlated, (p less than 0.001), with the mean per cent of tumor cells showing glandular differentiation at each stage as follows: A--71 per cent; B--59 per cent; C--33 per cent; D--28 per cent. Analysis of variance revealed these differences to be significant (p less than 0.001), and Newman-Keuls test showed significant differences between the following stage pairs: A-C, A-D, B-C, B-D (p less than 0.05). In spite of the marked correlation between stage and grade, multiple regression analysis showed them to be independent predictors of survival, although their combined effect was not much greater than that of morphometric grading alone. We conclude that, for prostatic carcinoma, the close correlation of stage and grade makes it difficult to combine them in determining the prognosis of the individual patient, although both together may be useful in studies of large populations.

Adenocarcinoma↗
PubMed1984

Correlation of immunohistochemical markers with patient prognosis in breast carcinoma: a quantitative study.

In a series of 46 cases of primary mammary ductal carcinoma, immunohistochemical markers of differentiation (casein, human placental lactogen, alphalactalbumin, pregnancy specific beta-1 glycoprotein, secretory component, CEA, and peanut lectin agglutinins [PLA]), were quantitated via point-counting. An immunoperoxidase bridge (PAP) was used to identify all except the PLA, in which an avidin-biotin complex with alkaline phosphatase development was employed. For none of the markers was there any difference in the quantity present in tumors of patients who had recurred versus the tumors of patients who had enjoyed a minimum of five years disease-free survival. Nonneoplastic epithelium was only rarely positive for these markers. Although eventually surmounted, technical problems significantly hampered application of morphometry to this histochemical material. The authors conclude that these markers have little relationship to differentiation toward mammary duct epithelium and that they do not provide significant prognostic information in patients with breast cancer.

Arachis↗
PubMed1983

The prognostic significance of vascular channel involvement and deep stromal penetration in early cervical carcinoma.

Eighty-eight patients with FIGO Stage Ib and IIa squamous cell carcinoma of the cervix underwent radical hysterectomy with pelvic and paraaortic lymphadenectomy. The records and histopathologic material were reviewed to determine the prognostic significance of vascular channel involvement and deep stromal penetration by tumor. Seventy-four patients (84%) were alive and free of disease for more than 2 years and 14 (16%) developed recurrent carcinoma within that time. A positive correlation was found between depth of stromal penetration by tumor and the degree of vascular channel involvement (p less than 0.05). Vascular involvement in itself did not significantly affect nodal status, survival or the rate of recurrence. Depth of penetration was associated with a higher incidence of positive nodes (p less than 0.05). There was a trend towards a lower survival rate and a higher recurrence rate in patients with deep stromal penetration as compared to those with superficial tumors. Microscopic nodal disease increased the rate of recurrence and had an adverse effect on survival. The combination of deep tumor penetration and positive nodes in the same patient was associated with the highest recurrence rate and the lowest survival (p less than 0.05). Nodal status was a more significant prognostic indicator than depth of tumor penetration because patients with deeply penetrating tumors and positive nodes had more than twice the recurrence rate than did patients with deep tumors and negative nodes. Postoperative radiation therapy was beneficial to patients whose tumors demonstrated deep stromal penetration and microscopic metastases to pelvic lymph nodes.

Carcinoma, Squamous Cell↗
PubMed1983

Morphometric analysis of differentiation in human breast carcinoma. Tumor grading.

Subjective grading systems suffer from limited reproducibility and do not assign a sufficiently large proportion of patients to the most predictive grades (1 and 3). In 50 cases of stage 1 or stage 2 mammary ductal carcinoma having at least five-year follow-up, we quantitated the proportion of neoplastic cells showing glandular differentiation (DI) or remaining within ducts (IN). Patients who experienced recurrence had significantly less of both DI and IN, and the point at which 10% of neoplastic cells was composed of DI + IN appeared to be predictive for recurrence; ie, 24 recurrences appeared among the 33 patients who had tumors with DI + IN less than 10%, whereas none developed among the 14 patients having tumors with DI + IN greater than 10%. Only three patients could not be classified with this marker. Tumor stage and grade were independent variables. Reproducibility among three observers averaged 95%. The morphometric evaluation can be performed by a technician under the direction of a pathologist.

Adenocarcinoma, Mucinous↗
PubMed1983

Morphometric analysis of differentiation in human breast carcinoma. Tumor heterogeneity.

The assumption that tumor grading is best performed in the region having the least differentiation was tested in a series of mammary ductal carcinomas by quantitating the relative amounts of neoplastic cells that remain within ducts (intraductal tumor [IN]) or participate in glandular formations (differentiated infiltrating tumor [DI]). Field-to-field variation in these two elements displayed a linear correlation with their overall level in each tumor. Since having less than 10% DI + IN is a marker for recurrence among breast cancer patients, this marker was applied to find variant regions of potential biological importance. Such regions were common, but their distribution was random, and they varied so much within themselves that they were not significantly different from the remainder of the tumor. Furthermore, the existence of such poorly differentiated regions did not correlate with a poor prognosis. Grading should be performed on a sample that is representative of the entire tumor, rather than its least differentiated part.

Breast Neoplasms↗
PubMed1983

Benign osteoblastoma of the temporal bone.

Benign osteoblastoma is an uncommon tumor in the skull and particularly rare in the temporal bone. This article presents the clinical, radiologic, and pathologic findings of the fifth case known to involve the temporal bone, and only th second case limited to the temporal bone itself. Subtotal removal was performed following embolization of the tumor. The patient currently has no evidence of disease eighteen months following therapy. Benign osteoblastoma is rarely synchronously or metachronously associated with its malignant counterpart, osteosarcoma. Treatment should be conservative. Subtotal curettage is acceptable and often results in long-term resolution. Radiotherapy is not recommended unless the removal is incomplete and the consequences of local recurrence are serious, as in vertebral lesions. This lesion may be highly vascular, and preoperative embolization should be considered to minimize blood loss at surgery.

Adolescent↗
PubMed1981

Simultaneous (non-epidermoid) neoplasms involving the head and neck.

The phenomenon of multiple primary malignant neoplasms involving the head and neck is well documented. Epidermoid carcinomas constitute the majority of these neoplasms. Case reports are made of two patients with simultaneously occurring chronic reticuloendothelial malignancies and non-epidermoid tumors involving the head and neck. The first case is one of chronic lymphocytic leukemia (CLL) and metastatic primary retroperitoneal extragonadal seminoma, while the second is one of lymphocytic lymphoma (LL) and a carotid body tumor (CBT). The head and neck manifestations of metastatic seminoma, CBT, and CLL and LL are discussed. A review of the literature of the association of each of these entities to other tumors is presented. Also presented is the evidence for an increased incidence of malignancies associated with CLL and LL and the complicating factors introduced when reticuloendothelial malignancies occur simultaneously with head and neck neoplasms.

Carotid Body Tumor↗
PubMed1980

Twenty-three new human tumor lines established in nude mice.

Subcutaneous inoculation of 87 human tumors into athymic nude mice, including gastrointestinal (non-colon) tumors, germ cell-primitive cell tumors, kidney tumors, lower urinary tract tumors, malignant melanomas and several metastases from unknown primary sites, resulted in growth in primary transplants in 32 cases (36.8%). Take rates varied among the tumor categories, from 56% for malignant melanomas to 13% for lower urinary tract tumors. They also differed among recurrent tumors (50%), metastases (41%) and tumors of primary site (28%). 23 tumor lines were established, including five lines each from renal cell adenocarcinomas and malignant melanomas, two each from adenocarcinoma of the pancreas and Wilms' tumors and only line each from various tumors of the gastrointestinal, germ cell-primitive cell, lower urinary tract and primary site unknown categories. The frequency of line establishment was greater for recurrent tumors and metastases than for primary tumors. Tumor lines have been carried continuously up to passage 17 in one case. Time in primary transplant varied from 3 to 29 weeks for the individual tumors and the average primary transplant time varied from 5.8 to 14.7 weeks for the six tumor categories. The average time in passage varied among the established lines from 2.3 to 10.6 weeks. The average passage time for all tumor lines was 5.3 weeks, with those of recurrent tumor origin showing the shortest average (4.0 weeks) followed by lines of metastatic origin (5.4 weeks) and those of primary tumor origin (5.8 weeks).

Adenocarcinoma↗
PubMed1979

Metastasis of human tumors in athymic nude mice.

The incidence of metastasis of xenogeneic tumors transplanted to nude mice is controversial. We studied 106 malignant human tumor lines in a total of 1,045 nude mice, and observed metastasis in only 14 instances (1.3%), involving 11 different tumor lines. Three of the lines showed repeated metastasis. Breast tumor lines metastasized with significantly greater frequency than other tumor types. None of the sarcoma lines metastasized. Tumors derived from human metastases were no more prone to metastasizing in nude mice than were tumors derived from primary sites. However, deep penetration of the body wall during growth of the tumor transplant was highly correlated with metastasis (p less than 0.001). Such factors as nude mouse health, tumor size and growth rate, and age and sex of the host mouse were not correlated with metastasis. Serial passage in nude mice did not select for a more malignant tumor line, since the incidence of metastasis did not differ at various passage levels. Thus, metastasis of human malignant tumors in nude mice would appear to depend primarily upon the site of tumor growth in the nude mouse, and upon the intrinsic metastasizing capability of the tumor line employed.

Animals↗
PubMed1979

Establishment of human colon carcinoma lines in nude mice.

After subcutaneous inoculation into nude mice of 24 human colon adenocarcinomas, growth, defined as histopathologically confirmed tumor growth which has been passed, was observed in 13 cases (54%). Tumors from metastatic sites showed higher take rates (58%) than tumors from primary sites or recurrent tumors (50%). Nine continuous tumor lines were established (69% of growing tumors) with metastatic tumors establishing more readily (100% of growing tumors) than primary tumors (40%). The average period in primary transplant was shorter for metastasis (8.3 weeks), than for primary tumors (18.5 weeks); total material 10.6 weeks. Average periods between passages were shorter than primary transplant times; these periods were shorter for metastases (6.6 weeks) than for primary tumors (9.4 weeks); total material 7.4 weeks. Of four growing tumors not established as continuous lines, three were primary and one a recurrent tumor, and the loss of tumor growth occurred in very early passages, not later than passage 3. All nude mouse-grown colon tumors were moderately well differentiated.

Adenocarcinoma↗
PubMed1979

Primary neoplastic transformation in vivo of xenogeneic skin grafts on nude mice.

Rabbit skin was infected with Shope papilloma virus and grafted orthotopically to nude mice. Typical Shope rabbit papillomas developed in most of the grafts, but similarly treated nude mouse skin grafts were not altered. These results demonstrated that xenogeneic tissues retained susceptibility to oncogenic agents after transplantation to nude mice. The results also implied that it should be feasible to study carcinogenesis of human tissues in this system.

Animals↗
PubMed1979

Incidence and pathological features of spontaneous tumors in athymic nude mice.

Systematic observation of 1141 nude mice (Swiss background [corrected] strain) that received human tumor transplants revealed 24 spontaneous tumors, 18 of lymphoreticular origin and 6 pulmonary adenomas. Spontaneous tumors were seen at an average age of 9.1 months, and 22 of the tumors were seen only in that fraction of our group (324 mice) surviving for 5 months or more (22 of 324 X 100 = 6.8%). Transplantation of these tumors to other nude mice was successful in three of five cases. Mice transplanted with adenocarcinoma of the colon and with tumors of the urogenital tract developed spontaneous tumors more often than did mice receiving other types of human tumor transplants. Progressive growth of the human tumor transplant occurred significantly less often in the mice that eventually developed spontaneous tumors than in the mice that showed no spontaneous tumor development. Nevertheless, the incidence of spontaneous tumors in these nude mice was similar to that reported for the thymus-bearing background strain.

Adenoma↗