Low MIB-1 Labeling Index Research Articles

Low-Dose Acetylsalicylic Acid Treatment in Non-Skull-Base Meningiomas: Impact on Tumor Proliferation and Seizure Burden.

Simple SummaryMIB-1 index is an established immunohistochemical marker reflecting the proliferative potential in meningiomas. Cyclooxygenase-2 has been demonstrated to be positively correlated with MIB-1 index in meningiomas. In a recent investigation, we revealed that cranial non-skull-base meningiomas have increased proliferative potential and increased inflammatory burden compared to other anatomical locations of meningiomas. The role of nonsteroidal anti-inflammatory drugs (NSAIDs) regarding proliferative activity and location-specific symptoms in non-skull-base meningiomas is unclear so far. In the present investigation, we therefore analyzed the impact of low-dose (100 mg) acetylsalicylic acid (ASA) treatment on the MIB-1 index and baseline symptomatic epilepsy. We identified that elderly female non-skull-base meningioma patients with ASA intake had significantly lower MIB-1 indices. Furthermore, ASA intake significantly reduced the preoperative seizure burden in non-skull-base meningioma. We believe that further research on NSAID treatment in non-skull-base meningiomas is necessary to enhance a tailored treatment scheduling.MIB-1 index is an important predictor of meningioma progression and was found to be correlated with COX-2 expression. However, the impact of low-dose acetylsalicylic acid (ASA) on MIB-1 index and clinical symptoms is unclear. Between 2009 and 2022, 710 patients with clinical data, tumor-imaging data, inflammatory laboratory (plasma fibrinogen, serum C-reactive protein) data, and neuropathological reports underwent surgery for primary cranial WHO grade 1 and 2 meningioma. ASA intake was found to be significantly associated with a low MIB-1 labeling index in female patients ≥ 60 years. Multivariable analysis demonstrated that female patients ≥ 60 years with a non-skull-base meningioma taking ASA had a significantly lower MIB-1 index (OR: 2.6, 95%: 1.0–6.6, p = 0.04). Furthermore, the intake of ASA was independently associated with a reduced burden of symptomatic epilepsy at presentation in non-skull-base meningiomas in both genders (OR: 3.8, 95%CI: 1.3–10.6, p = 0.03). ASA intake might have an anti-proliferative effect in the subgroup of elderly female patients with non-skull-base meningiomas. Furthermore, anti-inflammatory therapy seems to reduce the burden of symptomatic epilepsy in non-skull-base meningiomas. Further research is needed to investigate the role of anti-inflammatory therapy in non-skull-base meningiomas.

Clinical and cytopathological characteristics of HTLV-1+ hodgkin lymphoma.

BackgroundHuman T‐lymphotropic virus‐1 (HTLV‐1)+ Hodgkin lymphoma (HL) is difficult to differentiate from adult T‐cell leukemia/lymphoma (ATLL) with HL‐like histology (HL‐like ATLL).MethodsCytological and immunohistological features, HTLV‐1 proviral DNA integration, and rearrangements of the T‐cell receptor (TCR) Cβ1 gene were examined in 11 HTLV‐1+ patients with HL‐like disease.ResultsSix patients were classified as HTLV‐1+ HL and five as HL‐like ATLL in accordance with genetic findings of HTLV‐1 proviral DNA integration and rearrangements of the TCR Cβ1 gene. Small ordinary looking lymphocytes with round nuclei were detected in the background of six patients with HTLV‐1+ HL, which were immunohistochemically negative for CD25 and CC chemokine receptor (CCR)4 and had a low MIB1 labeling index (mean: 28.3%). In the HL‐like ATLL specimens, small‐ and medium‐sized atypical lymphocytes with indented and irregular‐shaped nuclei were found, and were diffusely positive for CD25 and CCR4, with high MIB1 labeling (mean: 76%). Both groups had scattered CD30+ and CD15+ Hodgkin and Reed Sternberg (RS) giant cells, with or without CD20 expression and Epstein‐Barr virus infection. The 50% overall survival period was significantly longer for the HTLV‐1+ HL group (180 months) than for the HL‐like ATLL group (7.8 months; P = .004).ConclusionsHTLV‐1+ HL showed typical small lymphoid cells with a low MIB1 labeling index in a background of Hodgkin and RS cells, with some scattered CD25+ and CCR4+ lymphocytes. In HTLV‐1 endemic areas, distinguishing HTLV‐1+ HL from HL‐like ATLL is important because of their differing treatment strategies and prognoses.

MON-628 Noninvasive Encapsulated Papillary RAS-Like Thyroid Tumor (NEPRAS) as a Possible Novel Subtype of Borderline Tumor

Background: A subset of thyroid tumors was classified into borderline/precursor tumors in the latest World Health Organization (WHO) classification. However, these tumors were defined only in terms of follicular structure, including hyalinizing trabecular tumor (HTT), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and uncertain malignant potential (UMP). As papillary microcarcinoma was proposed to be renamed to papillary microtumor (PMiT), there would be no reasons for restricting borderline/precursor tumors to the follicular growth pattern. Clinical Case: A 26-year-old man was incidentally found to have a 23 mm nodule in his thyroid. After undergoing left lobectomy, histological findings revealed extremely delicate nuclear changes in a noninvasive encapsulated papillary growth-patterned tumor. Tumor cells showed nuclear enlargement, irregularity, elongation, and overlapping as well as a few nuclear grooves. Nuclear pseudoinclusions were absent and chromatin characteristics were insufficient (nuclear score 2 according to Nikiforov et al. (1)). The patient was diagnosed with an encapsulated conventional papillary thyroid carcinoma by a local pathologist; however, a second-opinion consultation endorsed a follicular adenoma with papillary hyperplasia. In a third-opinion consultation, immunohistochemical analyses revealed a low MIB-1 labeling index and negative staining for cytokeratin 19 and BRAFV600E, which supported the expected indolent clinical behavior. Remarkably, mutational analysis identified a heterozygous point mutation of the KRAS gene but not the BRAF genes. Eventually, we speculated that this tumor could be a possible example of a novel borderline tumor with a papillary architecture, which does not qualify as NIFTP or UMP under the current WHO criteria. The patient refused additional surgery (complete thyroidectomy), and developed no recurrence or distant metastasis for 24 months. Conclusion: We reported a significant observer variation in a noninvasive encapsulated papillary growth-patterned tumor with delicate nuclear changes and a KRAS mutation. We speculated that our case could be an example of a novel borderline tumor with a papillary structure. Further studies using a larger number of patients are needed to elucidate this disease entity, because the possible introduction of terminology such as “noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)” without the word “cancer” could relieve psychological burdens of the patients similar to NIFTP. Reference: (1) Nikiforov YE, et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol. 2016;2:1023-9.

Encapsulated Papillary Thyroid Tumor with Delicate Nuclear Changes and a KRAS Mutation as a Possible Novel Subtype of Borderline Tumor.

Although papillary thyroid carcinoma (PTC)–type nuclear changes are the most reliable morphological feature in the diagnosis of PTC, the nuclear assessment used to identify these changes is highly subjective. Here, we report a noninvasive encapsulated thyroid tumor with a papillary growth pattern measuring 23 mm at its largest diameter with a nuclear score of 2 in a 26-year-old man. After undergoing left lobectomy, the patient was diagnosed with an encapsulated PTC. However, a second opinion consultation suggested an alternative diagnosis of follicular adenoma with papillary hyperplasia. When providing a third opinion, we identified a low MIB-1 labeling index and a heterozygous point mutation in the KRAS gene but not the BRAF gene. We speculated that this case is an example of a novel borderline tumor with a papillary structure. Introduction of the new terminology “noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)” without the word “cancer” might relieve the psychological burden of patients in a way similar to the phrase “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).”

Uterine cervical mesonephric hyperplasia with focal cystic change masquerading clinicopathologically as lobular endocervical glandular hyperplasia to malignancy

IntroductionAlthough uterine cervical mesonephric hyperplasia (MH) arising from mesonephric remnants is a well-known but uncommon entity, it might pose a clinicopathological diagnostic challenge to distinguish from lobular endocervical glandular hyperplasia (LEGH) or adenocarcinoma, if MH rarely presents as a lobular and/or cystic mass with expansion of the cervical wall. However, few papers have described the detailed clinicopathological characteristics of MH compared to those benign to malignant lesions. Case presentationAn early forties Japanese female presented with a history of increased vaginal watery discharge. Multiple cystic lesions measuring less than 3 mm in diameter generated a high signal intensity on T2-weighted MRI, in the bilateral aspects of the variably enlarged uterine cervix. A gross examination of a hysterectomy specimen revealed bilateral small multicystic lesions, filled partly with secreted fluids, measuring approximately 25 × 7 × 5 mm, respectively, located in the superficial to relatively deep cervical wall. A microscopic examination showed that these lesions predominantly consisted of a lobular proliferation of small to medium-sized tubules and cysts containing occasionally periodic acid-Schiff-positive eosinophilic/pink secreted materials, lined by bland-looking cuboidal to flattened epithelium. Immunohistochemically, these lining cells were specifically positive for CD10 in a characteristic luminal staining pattern, whereas negative for MUC6, and had a low MIB-1 labeling index. We ultimately made a diagnosis of cervical MH, lobular type, with focal cystic change. ConclusionWe should be aware that, since gynecologists/pathologists might misinterpret MH as LEGH to malignancy, including the malignant counterpart of MH, a wide panel of immunohistochemical antibodies can be helpful supplemental tools.

Epithelioid schwannoma of the skin displaying unique histopathological features: a teaching case giving rise to diagnostic difficulties on a morphological examination of a resected specimen, with a brief literature review

BackgroundEpithelioid schwannoma as a rare variant poses a challenge to all pathologists, as this uncommon entity is extremely difficult to conclusively diagnose by morphological analyses on a resected sample alone owing to its unique histopathological features. However, few papers have described the detailed clinicopathological characteristics of epithelioid schwannoma.Case presentationA 65-year-old female presented with a history of a flat and slightly elevated firm and tan plaque accompanied by occasional tenderness, measuring 10 × 8 mm, in the right joint of her hand 1 year before resection. A gross examination of a locally resected specimen revealed an encapsulated nodular lesion, yellow-whitish in color, partly filled with blood. A microscopic examination showed that the tumor predominantly consisted of a solid proliferation of epithelioid cells having mildly enlarged and round to partially spindled nuclei and abundant vacuolated or clear cytoplasm with very few mitotic figures and modest nuclear size variation, associated with focal hyalinized, cystic and hemorrhagic degeneration. This well-demarcated tumor was surrounded by dense, hyalinized and layered fibrocollagenous stroma. Immunohistochemically, these tumor cells were diffusely positive for S-100 protein and had a very low MIB-1 labeling index, and type IV collagen was strongly reactive with reduplicated basal lamina of them. We ultimately made a diagnosis of cutaneous epithelioid schwannoma.ConclusionWe should be aware that, since pathologists might misinterpret epithelioid schwannoma as other soft tissue tumors, including its malignant counterpart, a wide panel of immunohistochemical antibodies can be powerful supplementary tools for identifying a very rare entity of conventional schwannoma.

Chordoid glioma in suprasellar location with extension into the third ventricle: Smear preparation morphology of a rare tumor

We report a rare case of recurrent chordoid glioma in suprasellar region with extension into the third ventricle diagnosed peroperatively. On MRI, a brilliantly contrast enhancing lesion in the suprasellar region extending superiorly into the third ventricle and measuring 2.5 × 3 × 3.5 cm was identified. Patient had a previous history of subtotal removal of the tumor 8 months back and had received 56 Gy of postoperative radiotherapy. On smear preparation the tumor was composed of cells arranged in chords and rows in a myxoid background with sprinkling of lymphocytes. The individual cells were polygonal with moderate amount of faintly eosinophilic cytoplasm with cytoplasmic vacoules in few cells. The nuclei showed fine chromatin with small prominent nucleoli. Paraffin sections confirmed the diagnosis and on immunohistochemistry the tumor cells showed strong positivity for GFAP and focal weak positivity for EMA with low MIB-1 labeling index (<1%). To the best of our knowledge this is the first documented case of chordoid glioma described on crush cytology.

Multi-focal Myxopapillary Ependymoma in the Lumbar and Sacral Regions Requiring Cranio-spinal Radiation Therapy: A Case Report

Ependymomas are uncommon tumors that arise in the brain, spinal cord or cauda equina. Myxopapillary ependymomas is located exclusively in the conus medullaris or cauda equina, or film terminale region. In most myxopapillary ependymomas, the histological examination reveals low mitotic activity that is associated with a low MIB-1 labeling index (LI). The prognosis is generally favorable, when the appropriate treatment, including a total resection, is performed. The authors encountered a 39-year-old man with multifocal type of myxopapillary ependymomas compressing the cauda equina from the L2 to L3 level and L5-S1 level. A subtotal resection of the tumor was carried out. The histological examination revealed extremely high mitotic activity with a MIB-1 LI of 9.1%. Therefore, cranio-spinal radiation was added after surgery. The postoperative course was uneventful over the 3.5 year follow-up period.

Practical value of MIB-1 index in predicting behavior of astrocytomas

The MIB-1 labeling index (LI) has proved to be useful in assigning grading and prognosis to astrocytomas. The purpose of our study was to analyze the utility of MIB-1 LI in differentiating astrocytomas of varying grades and the possible relationships of MIB-1 LI with clinical parameters like age and sex. We also wanted to study the prognostic role of MIB-1 index in predicting behavior of astrocytomas. Our study included 145 patients with astrocytic tumors of varying grades. Immunolabeling for all patients was done using MIB-1 antibody. Survival data could be obtained for 64 patients. A Mann-Whitney U test was used to test the difference in MIB-1 LI between different histological grades. The univariate analysis was done by the Kaplan-Meier method, and the multivariate analysis for survival was performed using the Cox proportional hazard model. Significant differences were noted in mean MIB-1 LI of high-grade and low-grade diffuse astrocytomas. MIB-1 LI did not vary significantly with age and sex. Univariate analysis showed favorable prognostic factors for low histopathological grade, young patient age and low MIB-1 LI; however, multivariate analysis showed that only histopathological grade had independent prognostic significance. Our study proves that MIB-1 LI is not dependent on factors like age and sex and is solely dependent on histological grade. Though the average level of MIB-1 LI varies considerably in the different grades of astrocytomas, considerable overlap can be observed between them. MIB-1 LI is a very useful adjunct to the histopathological diagnosis and can be of great help in situations where the clinical and radiological findings do not correlate with histological diagnosis.

Oncocytic choroid plexus carcinoma: case report

Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic transformation. A 13-month-old girl presented with acute lethargy which quickly progressed to coma. A CT scan of the head revealed impending herniation due to hemorrhage within an intracranial tumor. An MRI scan showed a large, partly cystic and highly vascular left lateral ventricular mass. A near total resection was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma with extensive oncocyti c transformation. A minor portion of the moderately to poorly differentiated tumor exhibited classical microscopic features of choroid plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10 HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the large, eosinophilic, cytologically malignant but granular-appearing oncocytes comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with oncocytic transformation has not been previously reported. The remarkable extent of this alteration and its clinical significance remains to be determined.

Intracranial kaposiform hemangioendothelioma: proposal of a new malignant variant

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy and early childhood that occurs mainly in soft tissue and the retroperitoneum. The pathological characteristics of a KHE are fascicles of spindleshaped endothelial cells and slitlike vascular channels with irregular tumor margins. In spite of benign features such as rare mitoses and a low MIB-1 labeling index, a KHE is categorized as an intermediate malignancy because of local invasiveness into adjacent lymph nodes or organs. Resection is the treatment of choice for this type of tumor and adjuvant medical therapy is prepared for the tumor remnants and the associated Kasabach-Merritt syndrome. In this paper the authors report a case of a KHE without Kasabach-Merritt syndrome arising from the right tentorium cerebelli in a 13-month-old male child. The biological behavior of the tumor, including its pathological traits and clinical course, was malignant in nature. This case may be not only the first intracranial extraaxial KHE, but also the first truly malignant variant. Kaposiform hemangioendothelioma should be considered in the differential diagnosis of intracranial and extraaxial tumors.

The Predictive Value of CK19 and CD99 in Pancreatic Endocrine Tumors

Prediction of behavior in pancreatic endocrine tumors (PETs) is reliant on clinicopathologic features. However, there remains a cohort of PETs that behave aggressively despite showing indolent pathologic features. Recently, it has been suggested that CK19 and CD99 are sensitive ancillary markers that predict outcome in PETs. An analysis of 54 PETs and 2 resected liver metastases was undertaken to examine the relationship of CK19 and CD99 and the pathologic criteria in the WHO classification of PETs. CK19 was found to correlate with mitotic count (>5/50 high-power fields), an MIB-1 labeling index of > or =2%, lymphovascular/perineural permeation, lymph node involvement, and liver spread. Although not statistically significant, CK19-negative tumors tended to be smaller than the average tumor size in the series (2.5 vs. 3.6 cm). CD99 did not show any significant correlation with any of the WHO criteria. Tumors that are confined to the pancreas with low mitotic count and MIB-1 labeling index, tended to be CD99-positive. Both CK 19 (negative) and CD99 (positive) correlated with insulin-positive PETs. In conclusion, CK 19 may prove to be a useful ancillary diagnostic test in the routine work-up of PETs. CD99 does not appear to be as useful. There is no compelling evidence, from our study, to suggest that both these markers may be used in concert to predict the behavior of PETs.

Clear cell Meningioma, an uncommon variant of meningioma: a clinicopathologic study of nine cases

Clear cell meningioma (CCM) is an uncommon variant of meningioma, which affect younger patients, occur more often in spinal or cerebello pontine locations and shows a higher recurrence rate. Only few case reports have been described in the literature. The study has been undertaken to document the clinicopathological features of nine cases of CCM, operated at All India Institute of Medical Sciences during 1998 to December 2005. Clinical information was retrieved from the records of our Neurosurgery Department. The cases were stained with H&E, periodic Acid Schiff (PAS) with and without diastase. Immunohistochemistry for pancytokeratin, epithelial membrane antigen, vimentin, glial fibrillary acidic protein, and MIB-1 was done in all cases. During a period of 8 years, nine cases of CCM were diagnosed. Age ranged from 10 to 65 years (median age 26.0 years) with female predominance. Most common location was posterior fossa (CP angle). Clinically most of the patients presented with history of headache and features of cranial nerve palsies. The duration of symptoms varied from 3 to 60 months (mean 16.7 and median of 4 months). Radiologically lesions showed homogenous enhancement and were isointense to brain parenchyma. Histopathologic examination revealed tumor cells to be arranged in sheets with clear cytoplasm and monomorphic nuclei. MIB-1 labeling index (LI) ranged from 2 to 12% with a mean of 9%. Follow up varied from 3 to 84 months (median 36 months) and recurrence was noted in two patients after 2 and 3 years of surgery, respectively, despite their low MIB-1 labeling indices. CCM is a rare variant of meningioma with poor outcome. Less than 50 cases have been described in the literature. Low rate of recurrence and recurrence despite their low MIB-1 LI are some of the features, which needs to be documented. Hence, larger number of cases with adequate follow-up data need to be studied further to establish the clinical significance of this variant.

The Extrahepatic Bile Duct Lesions in End-Stage Primary Sclerosing Cholangitis

We examined histologically the bile duct lesions from 53 patients with end-stage primary sclerosing cholangitis (PSC) and compared them with similar lesions found in 25 surgically excised carcinomas of the extrahepatic bile ducts not associated with PSC. Of the 53 cases of PSC, 50 bile ducts were obtained at liver transplantation, two common bile ducts were segmentally resected for almost complete obstruction, and the entire extrahepatic biliary tract of another case was obtained at autopsy. Twenty bile ducts from patients who died without evidence of biliary tract disease served as controls. A modest increase in the number of intramural glands (mild hyperplasia) was noted in 13 cases (24.5%) of PSC. A marked increase in the number of intramural glands (florid hyperplasia) was found in 14 cases (26.4%) of PSC. In one case of florid hyperplasia, there was perineural and intraneural invasion of benign hyperplastic glands, which still maintained their lobular pattern. All cases of florid hyperplasia of intramural glands were accompanied by extensive fibrosis and marked nerve proliferation. Three of 24 (12.5%) invasive adenocarcinomas of the extrahepatic bile ducts showed mild hyperplasia of intramural glands without excessive nerve proliferation. Four invasive adenocarcinomas and one in situ carcinoma of the extrahepatic bile ducts showed florid hyperplasia of intramural glands (16%). The hyperplastic intramural glands were p53 negative and had low proliferative activity as measured by the low MIB-1 labeling index. In contrast, both in situ and invasive carcinoma expressed p53 protein and had a high MIB-1 labeling index. Focal high-grade dysplasia was found in one case of PSC (1.8%) and a small invasive adenocarcinoma in another (1.8%). Hyperplasia of intramural glands of the extrahepatic bile ducts is a reactive process that lacks specificity and is part of the morphologic spectrum of end-stage PSC. The incidence of dysplasia in PSC is low. Small invasive adenocarcinomas may be incidentally found in end-stage PSC, and detecting their presence before liver transplantation may be impossible.

Expression of E-cadherin, b-catenin, and Ki-67 in goblet cell carcinoids of the appendix: an immunohistochemical study with clinical correlation.

Goblet cell carcinoid (GCC) of the appendix is a rare entity, of which both the histogenesis and biologic behavior remain controversial, and prognostic tools and therapeutic strategies for this unusual tumor have yet to be defined. The aim of this study was to analyze expression of E-cadherin and b-catenin in GCCs of the appendix with long-term follow-up data as related to the expression of Ki-67 proliferation marker to provide a rationale for treatment guidelines. We analyzed the expression of E-cadherin, b-catenin, and Ki-67 in 11 GCCs of the appendix and control groups of typical carcinoids of the large intestine (n = 29), well to moderately differentiated adenocarcinomas of the colon (n = 10), poorly differentiated adenocarcinomas of the colon (n = 12), and normal appendiceal tissues (n = 10). There was no significant difference between the GCCs and normal appendiceal tissues regarding the expression of E-cadherin or b-catenin (p = 0.297 and 0.103, respectively). The percentage of positive GCC cells ranged between 0.52 and 10.35% (4.27 +/- 0.80), and only one case had a score >10%. Metastatic tumor spread and death were found in high MIB-1 labeling index (LI) cases of GCC (>3%). Our findings suggest that the behavior of the majority of GCCs might be indolent and different from adenocarcinomas because of the preserved expression of E-cadherin and b-catenin and relatively low MIB-1 LI. However, some of these tumors act aggressively and MIB-1 LI might be a good parameter to determine the therapeutic procedure.

Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas

Histologic grading of meningiomas has prognostic and clinical therapeutic implications. Meningiomas were histologically classified into 3 different World Health Organization grades. Grade II, an atypical meningioma, was defined by major and various minor histologic criteria. However, these histologic criteria sometimes are not fulfilled, and other criteria are necessary. We studied and analyzed the immunohistochemical expression of MIB-1, p53, p21WAF1, p27KIP1 proteins in 146 cases of meningiomas, including 109 benign, 27 atypical, and 10 anaplastic meningiomas. Most of the benign meningiomas expressed low MIB-1 labeling index (mean, 1.5%), and fewer cases had p53 protein expression. In contrast, the anaplastic meningiomas had a high labeling index of MIB-1 (mean, 19.5%) and always expressed p53 protein, with a mean labeling index of 6.3%. The atypical meningiomas had MIB-1 and p53 labeling indexes in the range between benign and anaplastic meningiomas, with mean labeling indexes of 8.1% and 3.5%, respectively. These expressions were statistically significant among benign, atypical, and anaplastic meningiomas (P <.001). We conclude that the immunohistochemistry of MIB-1 and p53 protein will be valuable in discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases. In addition, we also found direct correlation of p21 and inverse correlation of p27 expressions in meningiomas with increasing histologic grade and proliferative index. HUM PATHOL 32:970-975. Copyright © 2001 by W.B. Saunders Company

Assessment of basal cell status andproliferative patterns in flat and papillary urothelial lesions: A contribution to the new who classification of urothelial tumors of the urinary bladder

In 1999, the World Health Organization (WHO) published a newclassification of papillary urothelial tumors of the urinary bladder. Intended to represent a reproducible, easy-to-use classification system that better separates patients with true malignancies (bladder cancer) from those patients who are at an increased risk for developing bladder cancer, problems in the differential diagnosis of various lesions remained. Probably the most critical distinction is between papillomas, papillary urothelial neoplasms of low malignant potential (imp), and grade I papillary carcinomas. Conversely, problems in the distinction between reactive atypia, atypia of unknown significance, and dysplasia, as well as the distinction of dysplasia from carcinoma in situ (CIS), are unresolved. Whether urothelial basal cell status assessment on hematoxylin and eosin-stained slides completed by cytokeratin immunohistochemistry with anticytokeratin clone 348E12 may help to improve some of the previously mentioned diagnostic dilemmas was investigated. Basal cell status assessment was helpful in the differentiation between dysplasia and CIS. In dysplasia, CK IHC showed a predominantly basal labeling pattern, whereas in CIS, labeling of all urothelial layers was seen. Basal cell status assessment could separate 2 groups of pTa GIb papillary carcinoma. Group 1 with a continuous basal CK labeling and a low MIB-1 labeling index (LI) was compared with group 2, with a diffuse labeling pattern and a significantly higher M1B-1 LI. Whether group 1 carcinomas should better be assigned to the group of papillary urothelial neoplasms of Imp is discussed.

MIB-1 Immunoreactivity Correlates with Blood Vessel Density and Survival in Disseminated Malignant Melanoma

The purpose of our current work was to evaluate the prognostic significance of tumor cell proliferation in advanced metastatic melanomas and to investigate a possible correlation between the proliferation index and blood vessel density in metastatic tissue. Sixty patients with disseminated malignant melanoma treated with four-drug chemotherapy combined with interferon-α were included in this study. Proliferative activity and vascularity in metastatic tissues were examined by immunohistochemistry with anti-Ki-67 (MIB-1) and anti-CD31 antibody, respectively. A significant relationship between MIB-1 index and blood vessel number was detected (rho = 0.323, p = 0.013). In survival analysis, the overall survival and disease-free survival were significantly longer (58 and 38 vs. 38 and 17 months) for patients with low MIB-1 immunoreactivity (p = 0.012 and p = 0.023, respectively). Likewise, the low MIB-1 labeling index was associated with the prolonged survival calculated from the initiation of the chemoimmunotherapy (12 vs. 7 months, p = 0.032). In multivariate Cox’s proportional hazard analysis, MIB-1 positivity was an independent prognostic factor both for overall survival and for survival after beginning of the chemoimmunotherapy (p = 0.016 and p = 0.029).

Assessment of the expression of p53, MIB-1 (Ki-67 antigen), and argyrophilic nucleolar organizer regions in carcinoma of the extrahepatic bile duct

The authors retrospectively examined the predictive value of p53, MIB-1, and the argyrophilic nucleolar organizer regions (AgNOR) and examined the relationships among them in carcinoma of the extrahepatic bile duct (EHBD). Formalin fixed, paraffin embedded specimens from 54 patients with EHBD carcinoma were immunostained with MIB-1 against the Ki-67 nuclear antigen and p53 by the avidin-biotin peroxidase complex method, using the antigen retrieval technique of heating tissue sections in a microwave oven. The AgNOR proteins were localized at the optical level, as shown by a one-step silver staining technique. MIB-1 and AgNOR were closely associated with lymph node metastasis (P < 0.01). The cumulative survival rate for patients with a low MIB-1 labeling index (LI) (< 29%) was significantly better than that for patients with a high MIB-1 LI (> or = 29%) in cases of EHBD carcinoma (P < 0.05), but MIB-1 was not an independent prognostic factor in multivariate analysis. The results indicated that AgNOR and p53 overexpression had no prognostic value. The authors detected p53 in 24 of the 54 EHBD carcinomas (44.4%). There was a significant correlation between MIB-1 and AgNOR (P < 0.01). The authors found that neither MIB-1 nor AgNOR correlated with p53 overexpression. MIB-1 and AgNOR proved to be useful predictors of lymph node metastasis. The results of this study indicated that MIB-1 and AgNOR might be markers of the progression of EHBD carcinoma.

Assessment of the expression of p53, MIB‐1 (Ki‐67 antigen), and argyrophilic nucleolar organizer regions in carcinoma of the extrahepatic bile duct

BACKGROUND The authors retrospectively examined the predictive value of p53, MIB-1, and the argyrophilic nucleolar organizer regions (AgNOR) and examined the relationships among them in carcinoma of the extrahepatic bile duct (EHBD). METHODS Formalin fixed, paraffin embedded specimens from 54 patients with EHBD carcinoma were immunostained with MIB-1 against the Ki-67 nuclear antigen and p53 by the avidin-biotin peroxidase complex method, using the antigen retrieval technique of heating tissue sections in a microwave oven. The AgNOR proteins were localized at the optical level, as shown by a one-step silver staining technique. RESULTS MIB-1 and AgNOR were closely associated with lymph node metastasis (P < 0.01). The cumulative survival rate for patients with a low MIB-1 labeling index (LI) (<29%) was significantly better than that for patients with a high MIB-1 LI (≥29%) in cases of EHBD carcinoma (P < 0.05), but MIB-1 was not an independent prognostic factor in multivariate analysis. The results indicated that AgNOR and p53 overexpression had no prognostic value. The authors detected p53 in 24 of the 54 EHBD carcinomas (44.4%). There was a significant correlation between MIB-1 and AgNOR (P < 0.01). The authors found that neither MIB-1 nor AgNOR correlated with p53 overexpression. CONCLUSIONS MIB-1 and AgNOR proved to be useful predictors of lymph node metastasis. The results of this study indicated that MIB-1 and AgNOR might be markers of the progression of EHBD carcinoma. Cancer 1998;82:86-95. © 1998 American Cancer Society.