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Donatella Santini

Publications and source records attributed to Donatella Santini.

At least 19 recordsLinked to original sources
PubMed2006

p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres.

The comprehension of the basic biology of stem cells is expected to provide a useful insight into the pathogenesis of cancer. In particular, there is evidence that hypoxia promotes stem cell renewal in vitro as well as in vivo. It therefore seems reasonable that stem cell survival and hypoxia response are strictly connected at molecular level. We here report that the 66-kDa isoform of the SHC gene (p66Shc) is induced in a breast cancer cell line by the exposure to hypoxic environment and that it controls the expression of the stem cell regulatory gene Notch-3. Then, we show that p66Shc/Notch-3 interplay modulates self-renewal (by inducing the Notch-ligand Jagged-1) and hypoxia survival (by inducing the hypoxia-survival gene carbonic anhydrase IX) in mammary gland stem/progenitor cells, expanded in vitro as multicellular spheroids (mammospheres). We conclude that mechanisms that regulate stem cell renewal and hypoxia survival are integrated at the level of the p66Shc/Notch3 interplay. Because Notch-3, Jagged-1, and carbonic anhydrase IX are dysregulated in breast cancer, and because p66Shc is an aging-regulating gene, we envision that these data may help in understanding the relationship among aging, cancer, and stem cells.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer.

BACKGROUND: The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. METHODS: In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. CONCLUSION: The design of new approaches to identify such markers is warranted.

Adult↗
PubMed2006

Endocrine tumors of the ileum: factors correlated with survival.

AIM: To evaluate the most important factors correlated with survival in patients with endocrine tumors of the ileum, both at the time of diagnosis and during the follow-up period. METHODS: Fifty-nine patients with ileal endocrine tumors diagnosed in our institution between 1990 and 2004 were studied. RESULTS: The study included 36 men (61%) and 23 women (39%). The median age of the patients at the time of diagnosis was 61.4 (range 18-83) years. The median follow-up period was 71.9 (range 5-287) months. Forty patients (67.8%) were still alive at the end of the study; the median survival time was 172 months, and the 5-year survival rate was 78.9%. By univariate analysis, the survival rate was significantly related to female sex (p = 0.024) and flushing alone (p = 0.028) and associated with diarrhea at diagnosis (p = 0.015), weight loss at diagnosis (p = 0.038), Ki-67 level (p = 0.025), stage of disease at diagnosis (p = 0.012), presence of liver metastases at follow-up (p = 0.005), presence of diffuse metastases at diagnosis (p = 0.005) and at follow-up (p = 0.007), and type of surgical approach (overall: p = 0.018; not operated vs. radical surgery: p = 0.008; not operated vs. palliative surgery: p = 0.045). Using multivariate analysis, only female gender (p = 0.012) and the presence of liver metastases at follow-up (p = 0.004) were significantly related to survival. CONCLUSION: In the present study, female gender and the appearance of liver metastases at follow-up seem to be the main conditions which determine the poor prognosis of patients with ileal endocrine tumors.

Adolescent↗
PubMed2006

Enteric neuropathology of congenital intestinal obstruction: A case report.

Experimental evidence indicates that chronic mechanical sub-occlusion of the intestine may damage the enteric nervous system (ENS), although data in humans are lacking. We here describe the first case of enteric degenerative neuropathy related to a congenital obstruction of the gut. A 3-year and 9-mo old girl began to complain of vomiting, abdominal distension, constipation with air-fluid levels at plane abdominal radiology. Her subsequent medical history was characterized by 3 operations: the first showed dilated duodeno-jejunal loops in the absence of occlusive lesions; the second (2 years later) was performed to obtain full-thickness biopsies of the dilated intestinal loops and revealed hyperganglionosis at histopathology; the third (9 years after the hyperganglionosis was identified) disclosed a Ladd's band which was removed and the associated gut malrotation was corrected. Repeated intraoperative full-thickness biopsies showed enteric degenerative neuropathy along with reduced interstitial cells of Cajal network in dilated loops above the obstruction and a normal neuromuscular layer below the Ladd's band. One year after the latest surgery the patient tolerated oral feeding and did well, suggesting that congenital (partial) mechanical obstruction of the small bowel in humans can evoke progressive adaptive changes of the ENS which are similar to those found in animal models of intestinal mechanical occlusion. Such ENS changes mimic neuronal abnormalities observed in intestinal pseudo-obstruction.

Biopsy↗
PubMed2006

Solid-papillary tumors of the pancreas: histopathology.

A solid-pseudopapillary tumor is an uncommon and "enigmatic" pancreatic neoplasm, and the term encompasses the two most conspicuous histological features: solid and pseudopapillary areas. Grossly, it appears as a large solid, cystic or solid-cystic mass frequently having necrotic and hemorrhagic zones. Histologically, solid-pseudopapillary tumors are generally characterized by solid areas alternating with a pseudopapillary pattern, and cystic spaces which are the results of degenerative changes occurring in the solid neoplasm. Its immunohistochemical pattern is very distinctive and neoplastic cells are consistently vimentin-, CD10- and CD56-positive. Some cases express focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin, neuron-specific enolase and synaptophysin. Progesterone receptors are frequently present. Keratins are not expressed or are found only focally. Endocrine and pancreatic enzyme markers are absent; the origin of solid-pseudopapillary tumors has not yet been clarified. Many investigators favor the theory that solid-pseudopapillary tumors originate from multipotent primordial cells while others suggest an extra-pancreatic origin from genital ridge angle-related cells. Some controversy exists for both hypotheses. Solid-pseudopapillary tumors appear as a low malignancy tumor and only a small number of cases recur or develop metastases after resection. No pathological factors were found to correlate with the prognosis. Some histological features have recently been suggested to be associated with aggressive behavior.

CD56 Antigen↗
PubMed2006

Pancreatic solid-cystic papillary tumor: clinical features, imaging findings and operative management.

Solid-cystic papillary tumors of the pancreas are very rare and, until today, 718 cases have been reported in a review of the literature. Four patients affected by solid-cystic papillary tumors, observed in our Institute between January 1985 and July 2005, are reported. The clinicopathological, operative and survival data of this tumor were reviewed comparing our experience with a review of the literature. Solid-cystic papillary tumor have a preference for young women (age between 19-50 yrs) and show a large round, well-defined pancreatic mass(greater than 5 cm), clinically silent or with unspecific symptoms. The tumor is more frequently localized in the pancreas (80%) and is rarely a metastatic disease (20%). Surgical treatment with radical pancreatic resection of the tumor was performed in approximately 95% of the cases. In 467 patients, two-year survival was 97% (16 deaths) and 5-year survival was 95% (21 deaths). In conclusion, preoperative diagnosis of solid-cystic tumors of the pancreas is difficult but knowledge of its characteristic findings can aid in reaching a proper diagnosis. Surgery is the treatment of choice; it should be conservative in localized tumors, and aggressive, in non-localized tumors. The prognosis is very good, with long-term survival also in patients with metastases or unresectable tumors.

Adult↗
PubMed2006

HPV DNA patterns and disease implications in the follow-up of patients treated for HPV16 high-grade carcinoma in situ.

Twenty-five patients with high-grade cervical lesions associated with HPV16 infection were studied at the time of surgical treatment and followed up after conization. Before surgical treatment, the following parameters were analyzed: (1) physical status of HPV16 DNA, (2) viral load, (3) cytological presentation confirmed by histological diagnosis, and (4) colposcopy. At the time of conization, (5) margin presentation, and (6) cone biopsy were evaluated. At each stage of the follow-up (7) physical status of HPV16 DNA, (8) viral load, (9) cytological test, and (10) colposcopy were repeated. The correlation between the different parameters was examined. Significant differences in the viral loads were observed between integrated and episomal forms and between the coexisting integrated/episomal forms and the only episomal form, while no statistically significant differences were observed between integrated and coexisting forms. At the first stage of follow-up, 11 of 25 patients analyzed (44%) were negative to HPV DNA cytology and colposcopy tests, 13 of the 25 (52%) were HPV16 DNA negative, 17 (68%) cytology negative, and 20 (80%) colposcopy negative. At the closing stage, 15 of 25 subjects (60%) were negative to all three tests, 16 of the 25 (64%) were HPV16 DNA negative, 19 (76%) cytology negative, and 20 colposcopy negative (80%). These observations suggest that in surgery treated patients the viral clearance at the closing stage of follow-up was unrelated to the HPV DNA physical status and to the viral load before treatment, but was associated significantly with the effectiveness of surgery treatment, in particular with margin cone presentation.

Adult↗
PubMed2006

Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients.

The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments.

Adult↗
PubMed2006

Over-expression of topoisomerase IIalpha is related to the grade of cervical intraepithelial neoplasia (CIN) and high-risk human papillomavirus (HPV), but does not predict prognosis in cervical cancer or HPV clearance after cone treatment.

OBJECTIVE: One of the pathways leading to cervical cancer is a loss of normal cell cycle control. Topoisomerase IIalpha and IIbeta are important nuclear proteins controlling the G2/M checkpoint, and shown to be over-expressed in many human cancers. Their links to oncogenic human papillomavirus (HPV) types and their prognostic value in cervical cancer are practically unexplored. MATERIAL AND METHODS: As part of our HPV-PathogenISS study, a series of 150 squamous cell carcinomas (SCC) and 152 CIN lesions were examined using immunohistochemical (IHC) staining for topoisomerase IIalpha (topo IIalpha), and tested for HPV using PCR with three primer sets (MY09/11, GP5/GP6, SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV clearance/persistence after cone treatment. RESULTS: Topo IIalpha expression increased with increasing grade of CIN (p = 0.0001), with the most dramatic up-regulation upon progression from CIN2 to CIN3 and peaking in SCC (OR 16.23; 95%CI 7.89-33.38). Topo IIalpha up-regulation was also significantly associated with HR-HPV detection in univariate analysis (OR = 3.07; 95%CI 1.70-5.52), but was confounded by the histological grade (Mantel-Haenszel common OR = 1.622; 95%CI 0.782-3.365), and by entering both p16(INK4a) (9) and Survivin (33) in the multivariate regression model. Topo IIalpha did not predict clearance/persistence of HR-HPV after treatment of CIN, and it was not a prognostic factor in cervical cancer in either univariate or multivariate analysis. CONCLUSIONS: Over-expression of topo IIalpha is significantly associated with progression from CIN2 to CIN3, being a late marker of cell proliferation. Its close association with HR-HPV is plausibly explained by the fact that E7 oncoproteins of these HR-HPV (but not LR-HPV) block the normal pRb-mediated inhibition of topo IIalpha by degrading the wild-type Rb.

Antigens, Neoplasm↗
PubMed2006

Skin angiosarcoma arising in an irradiated breast: case-report and literature review.

BACKGROUND: Angiosarcoma (AS) is a rare, invasive malignancy originating from endothelial cells caused by many different clinical situations. AS following radiotherapy for breast cancer after conservative surgery is a rare but well-known association. OBJECTIVE: The aim of this article is to describe a case of AS after breast conserving surgery and to review the literature to date. RESULTS: We report the case of an 84-year-old woman who developed AS four years after she was subjected to quadrantectomy for invasive ductal cancer, followed by 30 tangent field radiotherapy sessions. She presented with a one-month history or red papular skin eruptions on the operated breast. Skin lesions were submitted for biopsy, and they were positive for AS. The patients was subjected to surgical excision of the remaining breast including all AS lesions. She is alive with no evidence of disease after 10 months follow-up. CONCLUSION: Post-radiotherapy AS is rare neoplasm, but it should be considered in the case of patients with red lesions after breast conserving surgery and adjuvant radiotherapy.

Aged, 80 and over↗
PubMed2005

Survivin as a marker of cervical intraepithelial neoplasia and high-risk human papillomavirus and a predictor of virus clearance and prognosis in cervical cancer.

We analyzed survivin as a marker of cervical intraepithelial neoplasia (CIN) and high-risk human papillomavirus (HR-HPV) and a predictor of HPV clearance and disease outcome in cervical cancer in 302 samples (squamous cell carcinomas [SCCs], 150; CIN lesions, 152) by immunohistochemical staining with survivin antibody and HPV testing using polymerase chain reaction. HR-HPV types were associated closely with CIN and SCC. There was a significant linear relationship between grade and intensity of survivin expression (P = .0001). Survivin overexpression also was associated strongly with HR-HPV type (P = .0001). Multivariate regression analysis revealed survivin and p16(INK4a) as equally strong independent predictors of HR-HPV. Deregulated survivin expression did not predict clearance or persistence of HR-HPV after treatment of CIN or survival in cervical cancer in univariate (P = .417) or multivariate analysis. After adjustment for HR-HPV, stage, age, and tumor grade in the Cox regression model, only stage (P = .0001) and age (P = .0001) remained independent prognostic predictors. Survivin seems to be an early marker of cervical carcinogenesis. Up-regulated survivin expression was an independent predictor of HR-HPV in cervical lesions, most plausibly explained by its normal transcriptional repression by wild-type p53 being eliminated by HR-HPV E6 oncoprotein.

Biomarkers, Tumor↗
PubMed2004

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma.

We applied comparative genomic hybridization (CGH) to 46 breast carcinoma samples, collected from 1993 to 1995, in order to detect chromosome 1q gains and 16q losses and to define whether samples showing both these alterations had distinct biopathologic features and different clinical outcome. A total of 22 samples (48%) had simultaneous chromosome 1q gain and 16q loss, which was always associated with other genetic changes. In total, 23 samples had various chromosome imbalances (including chromosome 1q gain independent of chromosome 16q loss and vice versa) and one sample did not show detectable alterations. Samples having chromosome 1q gain/16q loss were compared to the other samples with regard to neoplasm size, lymph-node status, histologic and nuclear grade, estrogen and progesterone receptor presence, Ki-67, pRB, Cyclin D1, Cyclin A, p53, p21 and p27 expression as detected by immunohistochemistry. The samples showing chromosome 1q gain/16q loss had high steroid hormone receptor expression (P=0.02), low cell growth fraction (Ki-67, P=0.03) and high p27 expression (P<0.001). No statistical correlation with disease-free survival and overall survival or response to hormonal therapy was found. We conclude that simultaneous chromosome 1q gain/16q loss is a frequent event in invasive breast cancer, which occurs in a subset of both intermediate- and high-grade breast carcinomas. Although the final chromosome 1q and 16q imbalances might have originated from different chromosome alterations in low- and high-grade samples, the gene-dosage effect might be important in conferring peculiar biopathologic characteristics to this subset of samples. The cytogenetic and molecular mechanisms underlying these chromosome changes deserve further investigations.

Adenocarcinoma↗
PubMed2004

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.

BACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Abdominal Pain↗
PubMed2004

Does acute alcoholic pancreatitis precede the chronic form or is the opposite true? A histological study.

OBJECTIVES: Whether acute alcoholic pancreatitis occurs in a normal pancreas or in a pancreas that has already been altered by chronic pancreatitis is unclear. Our objective is to clarify the relation between acute and chronic alcoholic pancreatitis by histologic study of the pancreas in a group of patients having a first attack of acute alcoholic pancreatitis. METHODS: From January 1989 to December 1999, 138 patients with acute pancreatitis, of whom 28 had alcoholic pancreatitis, were seen by us; in 21 of the latter 28 patients, it was the first attack. Of these 21, 6 underwent surgery for acute necrotic pancreatitis. In all 6 patients, adequate pancreatic biopsies were obtained during surgery. Tissue samples were prepared for histologic examination according to standard procedures. RESULTS: In all 6 patients, both acute necrotic and chronic lesions were found. The chronic lesions had characteristics of chronic calcifying pancreatitis and consisted of perilobular and intralobular fibrosis. loss of exocrine parenchyma, dilated interlobular ducts, and protein plugs within dilated ducts. CONCLUSIONS: This study suggests that acute alcoholic pancreatitis develops in a pancreas already affected by chronic pancreatitis. The hypothesis that in alcoholics chronic pancreatitis derives from acute pancreatitis is not supported by the present data.

Acute Disease↗
PubMed2004

Activation of the ERK/MAP kinase pathway in cervical intraepithelial neoplasia is related to grade of the lesion but not to high-risk human papillomavirus, virus clearance, or prognosis in cervical cancer.

We subjected 302 archival samples (150 squamous cell carcinomas [SCCs] and 152 cervical intraepithelial neoplasia [CIN] lesions) to immunohistochemical staining with extracellular signal-regulated kinase-1 (ERK1) antibody and human papillomavirus (HPV) testing with 3 primer sets. Follow-up data were available for all SCC cases and 67 CIN cases. High-risk (HR) HPV types were associated with CIN (odds ratio [OR], 19.12; 95% confidence interval [CI], 2.31-157.81) and SCC (OR, 27.25; 95% CI, 3.28226.09). There was a significant linear relationship between lesion grade and ERK1 staining intensity (P = .0001). ERK1 staining was a 100% specific indicator of CIN, with a 100% positive predictive value, but a poor predictor of HR HPV. ERK1 expression did not predict clearance or persistence of HR HPV after CIN treatment. ERK1 staining did not significantly predict survival in cervical cancer in univariate (P = .915) or multivariate analysis. After adjustment for HR HPV, stage, age, and tumor grade in the Cox regression model, only stage (P = .0001) and age (P = .002) remained independent prognostic factors. ERK1 expression seems to be an early marker of cervical carcinogenesis. ERK1 overexpression is not a specific marker of HR-HPV in CIN and cervical cancer, nor does it predict virus clearance after CIN treatment or disease outcome in cervical cancer.

Adolescent↗
PubMed2003

Retention of the p53 codon 72 arginine allele is associated with a reduction of disease-free and overall survival in arginine/proline heterozygous breast cancer patients.

PURPOSE: The arginine to proline substitution at codon 72 represents a common aminoacidic polymorphism of the p53 protein. Recent data suggest that p53 codon 72 may modulate the response to cancer therapy. The aim of this study was to test the hypothesis that the p53 codon 72 genotype, evaluated in the tumor tissue and in the disease-free lymph node, is related to differences in disease-free and overall survival among breast cancer-affected patients. EXPERIMENTAL DESIGN: We assessed the p53 codon 72 genotype in DNA from disease-free lymph nodes and neoplastic tissues obtained from 67 women affected by breast cancer who underwent surgical resection at the Bologna Breast Cancer Surgical Unit from 1993 to 1995. RESULTS: We found that the retention of the p53 codon 72 arginine allele in the tumor tissue of proline/arginine heterozygous breast cancer patients is associated with statistically significant reduced disease-free and overall survivals. CONCLUSIONS: Our findings suggest that the genotyping for p53 codon 72 locus in both the tumor tissue and in the lymph node of breast cancer patients could contribute to identify a subset of arginine/proline heterozygous patients who have a reduced survival that is associated with the specific retention of the arginine allele in the tumor tissue.

Adult↗
PubMed2003

Independent determinants of inaccuracy of colposcopically directed punch biopsy of the cervix.

OBJECTIVE: The goal of this study was to determine the clinical factors independently associated with inaccuracy of colposcopically directed punch biopsy in defining extent and severity of epithelial lesions of the cervix. METHODS: The study was conducted in a colposcopy clinic devoted to the management of patients with abnormal Pap smear and/or histology diagnosis of cervical intraepithelial neoplasia (CIN) on punch biopsy or endocervical curettage. Seven hundred and thirty-nine patients (median age, 33 years; range, 18-83 years) referred with a punch biopsy diagnosis of CIN2-3 and treated with electrosurgical conization were evaluated. Cone histology diagnosis was assumed to supply the correct diagnosis. Two types of deviation of biopsy diagnosis were considered: (1). unconfirmed high-grade CIN diagnosis, defined as a cone diagnosis of CIN1 and reactive/reparative changes, and (2). nondiagnosis of carcinoma, defined as a cone diagnosis of microinvasive and invasive squamous carcinoma. Multinomial logistic regression analysis was used to assess the determinants of the probability of each type of deviation. RESULTS: The probability of unconfirmed high-grade CIN diagnosis (n = 190, 25.7%) was inversely related to number of quadrants involved, severity of referral Pap smear, and grade of biopsy. The probability of nondiagnosis of carcinoma (n = 43, 5.8%) was positively related to patient age, invisibility of the squamocolumnar junction, number of quadrants involved, and cone width. Endo-ectocervical location, cone depth, and time period had no effect whatsoever. CONCLUSIONS: The study confirmed previous observations regarding the positive association of patient age and invisibility of squamocolumnar junction with the probability of nondiagnosis of carcinoma. The concomitant positive effects of number of quadrants involved and cone width were suggested to mirror the effect of circumferential development and, respectively, surface area of CIN. Severity of referral Pap smear and grade of biopsy were shown to be inversely related to the probability of a cone diagnosis of CIN1 and benign changes.

Adolescent↗