Sunanda Goswami

Use of thyroid transcription factor 1, PE‐10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine‐needle aspiration biopsy specimens

The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF‐1) and PE‐10 are fairly specific markers for primary lung tumors in histologic specimens. TTF‐1 regulates the expression of surfactant protein production, and PE‐10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors.

Estrogen and progesterone receptor expression in endometrial polyps.

Endometrial polyps are a frequent cause of abnormal uterine bleeding, but their pathogenesis is poorly understood. This study was undertaken to investigate if endometrial polyps result from localized overexpression of estrogen receptors (ERs) or reduced expression of progesterone receptors (PRs). Fourteen cases of endometrial polyps, in which normal cycling endometrium was also present on the same slide, were immunostained for ERs and PRs. Percentages of positive cells in glands and stroma for each receptor were subjectively assessed to the nearest 5%. The intensity of staining was recorded on a scale from 1+ to 4+. The level and intensity of staining in polyps were compared with the staining in normal endometrium. Fewer stromal cells in polyps expressed ERs and PRs compared with cycling endometrium (% ER = 55.9 +/- 25.8 vs. 74.3 +/- 25.8, p = 0.03; % PR = 56.1 +/- 28.2 vs. 87.5 +/- 10.1, p = 0.002). Stroma in polyps also had significantly reduced intensity of staining for PRs, but not for ERs (intensity PR = 2.7 +/- 1.4 vs. 3.5 +/- 0.7, p = 0.015; intensity ER = 2.1 +/- 0.7 vs. 2.4 +/- 0.8, p = 0.45). There were no significant differences in expression of ERs and PRs in the endometrial glands in endometrial polyps compared with normal endometrium (% ER = 75.4 +/- 32.5 vs. 70.7 +/- 39.2. p = 0.25; % PR = 79.6 +/- 32.8 vs. 80.4 +/- 34.4, p = 0.8; intensity ER = 2.7 +/- 0.9 vs. 2.4 +/- 1, p = 0.15; intensity PR = 2.9 +/- 1.4 vs. 3.4 +/- 0.7, p = 0.15). We conclude that endometrial polyps may result from a decrease in ER and PR expression in stromal cells. Because of these receptor-negative stromal cells, endometrial polyps may be relatively insensitive to cyclic hormonal changes.

Proliferating cell nuclear antigen (cyclin) expression in normal and abnormal cervical squamous epithelia.

Expression of Proliferating cell nuclear antigen (PCNA) was evaluated in formalin-fixed, paraffin-embedded normal and abnormal cervical squamous epithelia using immunoperoxidase stains and PC10 monoclonal antibody to PCNA. PCNA was exclusively expressed in the parabasal and basal layers of normal ectocervix and a similar pattern was seen in nine of the 11 cases with squamous metaplasia. Examples of cervical dysplasia showed expression in higher layers of cervical epithelium, corresponding to the degree of dysplasia. Increased staining was seen in condylomas and markedly reduced staining with atrophy. The percentage of basal cells that stained increased progressively from atrophic to normal, to condylomatous, to dysplastic epithelia. Proliferative activity can be satisfactorily assessed in formalin-fixed cervical epithelia using PC10 PCNA antibody. This assessment can be of potential diagnostic use in difficult cases.

Expression of metalloproteinases and tissue inhibitors of metalloproteinases in giant cell tumor of bone: An immunohistochemical study with clinical correlation

The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumors biological behavior, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded tissue was collected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had local recurrence. One showed metastasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 was strongly expressed in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy distribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 recurrent cases, TIMP-1 was expressed weakly by both giant and stromal cells. TIMP-2 was variably expressed in the giant cells of the nonrecurrent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell positivity for TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in the giant cells. These results indicate that expression of MMPs and TIMPs differs in giant cells and stromal cells in the same tumor. More significantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in the recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Finally, these markers may prove useful in predicting behavior in these tumors.

Comparison of p53 and MIB1 expression in benign and borderline areas of ovarian serous tumors

Ovarian serous tumors of borderline malignancy frequently show morphologically benign and borderline areas within the same tumor. This study was undertaken to determine if these two morphologically disparate areas differ in their proliferative activity and p53 expression. Formalin-fixed, paraffin-embedded archival tissue from 17 ovarian serous borderline tumors with morphologically benign and borderline areas were immunostained with monoclonal antibodies against p53 and MIB1. The percentage of positive cells was determined by counting 100 consecutive cells for each stain in the most intensely stained areas in morphologically benign and borderline portions of these tumors. There was a significantly increased proliferation (MIB1 expression) in borderline areas compared with benign areas (37.05 +/- 15.3 versus 12.88 +/- 6.7, p = 0.0001). More than 30% of cells were positive for MIB1 in 13/17 borderline areas compared with none of the 17 benign areas (p < 0.0001). The expression of p53 was also higher in borderline areas compared with benign areas (7.12 +/- 8.8 versus 2.94 +/- 4.46, p = 0.0078). More than 10% of cells were p53 positive in 5/17 borderline areas compared with 1/17 benign areas (p = 0.08). However, there was no significant correlation between p53 expression and MIB1 expression in either the benign or borderline areas (p = 0.4 and 0.2, respectively). In summary, morphologically borderline areas show significantly higher p53 expression and proliferation compared with morphologically benign areas in ovarian serous borderline tumors. Alterations of p53 may play a pathogenetic role in some ovarian serous borderline tumors. The lack of correlation between p53 expression and MIB1 expression, however, suggests involvement of other factors, in addition to p53, in determining the proliferative rate of ovarian serous borderline tumors.

Fascin expression in serous tumors of ovary correlates with aggressiveness of malignancy.

Ovarian serous tumors make up about one-fourth of all ovarian tumors. There is a spectrum of proliferation and cellular atypia in these tumors with benign serous cystadenoma, borderline tumors, and low grade or type I serous carcinoma at the lower end and type II or high-grade serous papillary cystadenocarcinoma at the higher end. Fascin is a globular actin cross-linking protein involved in cell motility that has been shown to be upregulated in many human neoplasms and associated with the aggressiveness of malignancy. The aim of this study was to investigate fascin expression in serous tumors of ovary and to evaluate its relationship with the aggressiveness of tumor. Sections from a total of 66 serous tumors of ovary were collected including 26 serous carcinomas, 20 borderline serous tumors, and 20 benign serous cystadenomas. Ten benign ovaries with inclusion cysts were used as controls. Sections were immunostained with fascin. Fascin expression was significantly increased in borderline (13/20, 65%) and malignant serous tumors (22/26, 84%) compared with benign serous cystadenoma (0/20) (P<0.001). There was increased quantitative expression of fascin in carcinoma compared with borderline tumors (diffuse versus patchy). Fascin expression also correlated well with the tumor grade in serous carcinoma cases with 8/12 (66%) of grade I/II tumors staining positive compared with all 14 (100%) of grade III tumors showing fascin expression (P<0.05). Our findings suggest that upregulation of fascin plays a role in increasing aggressiveness of serous ovarian tumors and could potentially be a molecular therapeutic target and a prognostic marker.

Gastrin-Releasing Peptide in Hypoplastic Lungs

The relative abundance of pulmonary neuroendocrine cells synthesizing gastrin-releasing peptide (GRP) was estimated for normal fetal lungs and hypoplastic lungs. Percentage of bronchiolar epithelial area staining positively with anti-GRP antiserum was computed for each case using a SAMBA 4000 image analyzer. The majority of hypoplastic lungs (10 of 12 cases) showed markedly diminished GRP immunoreactivity, which appeared to vary with etiology. Six cases of pulmonary hypoplasia associated with renal anomalies, three cases associated with hydrops, and one case of diaphragmatic hernia showed an average fivefold reduction in percentage of GRP immunostaining. A case of hypoplasia associated with Werdnig-Hoffmann disease had GRP immunoreactivity similar to that of controls, and GRP expression was markedly elevated (fivefold) in a case of hypoplasia with omphalocele.

Immunohistochemical profile of ovarian inclusion cysts in patients with and without ovarian carcinoma

SummaryThe expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance.