EGFR Mutation Testing: Changing Patterns of Molecular Testing in Brazil.

BACKGROUND: In Brazil, cancer is the second most common cause of death. Most patients in resource-limited countries are diagnosed in advanced stages. Current guidelines advocate for EGFR mutation testing in all patients with metastatic adenocarcinoma. Tyrosine kinase inhibitors are recommended in patients with advanced or metastatic disease harboring sensitizing mutations. In Brazil, there are limited data regarding the frequency of EGFR testing and the changes in patterns of testing overtime. MATERIALS AND METHODS: This was an observational, retrospective study. We obtained deidentified data from a commercial database, which included 11,684 patients with non-small cell lung cancer treated between 2011 and 2016 in both public and private settings. We analyzed the frequency of EGFR mutation testing over time. We also directly studied 3,664 tumor samples, which were analyzed between 2011 and 2013. These samples were tested for EGFR mutations through an access program to tyrosine kinase inhibitors in Brazil. RESULTS: Overall, 38% of patients were tested for EGFR mutations; 76% of them were seen in the private sector, and 24% were seen in the public center. The frequency of testing for EGFR mutations increased significantly over time: 13% (287/2,228 patients) in 2011, 34% (738/2,142) in 2012, 39% (822/2,092) in 2013, 44% (866/1,972) in 2014, 53% (1,165/2,184) in 2015, and 42% (1,359/3,226) in 2016. EGFR mutations were detected in 25.5% of analyzed samples (857/3,364). Deletions in Exon 19 were the most frequent mutations, detected in 54% of patients (463/857). CONCLUSION: Our findings suggest that the frequency of EGFR mutation in this cohort was lower than that found in Asia but higher than in North American and Western European populations. The most commonly found mutations were in Exon 19 and Exon 21. Our study shows that fewer than half of patients are being tested and that the disparity is greater in the public sector. IMPLICATIONS FOR PRACTICE: These data not only indicate the shortage of testing but also show that the rates of positivity in those tested seem to be higher than in other cohorts for which data have been published. This study further supports the idea that awareness and access to testing should be improved in order to improve survival rates in lung cancer in Brazil.

Microinvasive adenocarcinoma of the cervix in a young woman vaccinated against human papillomavirus: the screening must be continued.

OBJECTIVE: This report describes a case that illustrates the limitations of the vaccination screening process for human papillomavirus (HPV) infection. CASE: We report an unexpected microinvasive adenocarcinoma of the cervix arising in a young woman vaccinated against HPV as part of a clinical trial 6 years previously and followed up annually by cytology. In January 2012, at age 23 years, the patient received a cytological result of atypical squamous cells, cannot exclude high-grade cervical squamous intraepithelial lesion, and colposcopy showed slight abnormalities. Biopsy revealed an adenocarcinoma in situ. Conization of the cervix was performed, and the diagnosis was microinvasive adenocarcinoma. Polymerase chain reaction and immunohistochemical study of conization material showed positivity for HPV-18 L1, p16, and Ki-67. Retrospective analysis of the clinical trial information revealed that 7 HPV tests had been performed, and all were positive for HPV-18, including the sample collected before the first vaccination. CONCLUSIONS: HPV-18 was present in the cervix before vaccination. Persistent detection of HPV-18 should be considered an important factor in treatment planning. This case demonstrates the need to vaccinate women before their first sexual contact and highlights the need for keeping adequate screening even in vaccinated individuals.

Benign cervical schwannoma with tracheal invasion.

Schwannomas commonly develop in the cervical region, 25% - 45% of cases are diagnosed in this anatomical region. Tracheal neurogenic tumors are exceedingly rare and can be misdiagnosed as invasive thyroid carcinomas or other infiltrating malignancies when present at the level of the thyroid gland. Here, we present a case of synchronous benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma in a patient who was initially hospitalized for COVID-19. The patient presented with dyspnea that was later found to be caused by tracheal extension of a cervical tumor. Surgical excision was performed, and the surgical team proceeded with segmental tracheal resection, removal of the cervical mass, and total thyroidectomy. The specimen was sent for pathological analysis, which revealed synchronous findings of a benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma. The literature on this subject, together with the present case report, suggests that neurogenic tumors should be included in the differential diagnosis of obstructing tracheal cervical masses. Surgical excision is the first-line of treatment for benign cervical schwannomas.

Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status.

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.

Fibroblastic reticular cell tumour of the internal iliac lymph node presenting as a hypervascular lesion and mimicking a pseudoaneurysm: an extremely rare diagnosis.

A woman in her 50s presented with a rounded and hypervascular lesion in the right internal iliac lymph node chain, contacting with small branches of the anterior division of the internal iliac artery. Since the lesion matched the blood arterial pool in CT and the patient exhibited multiple vascular abnormalities that suggested segmental arterial mediolysis, a pseudoaneurysm hypothesis was initially made. Arteriography was realised due to the intention for embolisation of the pseudoaneurysm, but the dynamic behaviour during the exam suggested a hypervascular tumour more. An MRI was conducted, bringing new evidence, favouring the possibility of a neoplasm. The lesion excision was performed and sent to pathology. Morphological and immunohistochemical findings suggested a rare case of a fibroblastic reticular cell tumour of the internal iliac lymph node.

Genetic Ancestry of 1127 Brazilian Breast Cancer Patients and Its Correlation With Molecular Subtype and Geographic Region.

PURPOSE: Breast cancer molecular subtypes show significant differences in different ethnic groups in the United States, but no study has evaluated genetic ancestry in breast cancer in Brazilian women. METHODS: Breast cancer patients from distinct parts of Brazil were evaluated. Molecular subtypes were determined by immunohistochemistry. Genetic ancestry was evaluated using a panel of 46 AIMs (ancestry informative markers), which classified genetic ancestry as European, African, Asian, and Amerindian. PCR products were subjected to capillary electrophoresis and analyzed using GeneMapper 4.0 software. Ancestry was evaluated with Structure v.2.3.3 software. Ancestry was tested for correlations with geographic region and molecular subtype. The chi-square test and ANOVA with Bonferroni adjustment were applied. RESULTS: Genetic ancestry and clinical data were evaluated in 1127 patients. Higher rates of self-reported white ethnicity, European ancestry, and HER-2- luminal tumors were identified in the South region, which may influence age at diagnosis and result in a higher rate of early tumors. Conversely, higher rates of African ancestry in the North and Northeast regions, self-reported nonwhite ethnicity, HER-2+ tumors, and triple-negative tumors were noted. Triple-negative and HER-2+ tumors were associated with higher advanced and metastatic disease rates at diagnosis, with triple-negative tumors being more frequent in young women. CONCLUSION: Differences in genetic ancestry, self-reported ethnicity, and molecular subtype were found between Brazilian demographic regions. Knowledge of these features may contribute to a better understanding of age at diagnosis and the molecular distribution of breast cancer in Brazil.

Malignant mesothelioma of the tunica vaginalis testis: A rare cause of hydrocele.

Mesotheliomas of the tunica vaginalis testis are very uncommon tumors, with rare cases published in the literature. This report demonstrates a case in with such a tumor was diagnosed in a 50-year-old man who presented to the emergency room with mild, acute scrotal pain and swelling, without previously known scrotal pathology. It is noted that sonographers should be aware of the typical characteristics that allow for suspecting malignancy in scrotal sonography performed in the emergency setting; this was particularly important in this case. Surgical pathology analysis of the right radical orchiectomy specimen confirmed the diagnosis.

Surgically treated mediastinal fat necrosis: an exception to conservative treatment.

Mediastinal fat necrosis is an important differential diagnosis for acute chest pain in previously healthy patients. Imaging examination is essential to establish this diagnosis, as physical examination can be unhelpful and laboratory tests are non-specific. The treatment of choice is conservative, with non-steroidal anti-inflammatory drugs; surgery is reserved for a few selected cases. We present the case of a 37-year-old male patient with mediastinal fat necrosis, refractory to the conservative management and complicated by growing pleural effusion, which was treated surgically.

Consensus on Screening, Diagnosis, and Staging Tools for Prostate Cancer in Developing Countries: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Primary central nervous system peripheral T-cell lymphoma in a child.

A 10-year-old Caucasian boy was admitted to the hospital with a 3-month history of headache, vomiting, ataxia, and right amaurosis. A magnetic resonance imaging (MRI) showed a solid, expansive, parasagittal mass in the right parietal hemisphere that extended sagitally to include the optical chiasm. The lesion was considered unresectable. Histology and immunophenotyping of biopsy tissue revealed characteristics of peripheral T-cell lymphoma. No other anatomical region, including bone marrow, was compromised. Primary T-cell lymphomas of the central nervous system are rare, especially in childhood. Here, we describe the rapidly deteriorating and fatal clinical course of a boy with a primary T-cell lymphoma in the central nervous system.

Potential economic impact of the 21-gene expression assay on the treatment of breast cancer in Brazil.

OBJECTIVE: The 21-gene expression assay may support the decision regarding use of chemotherapy in early breast cancer. We sought to investigate the potential impact of incorporating the 21-gene expression assay into private practice in Brazil, from the perspective of third party payers. METHODS: We conducted a web-based survey with 30 (of a total of approximately 700) Brazilian medical oncologists, who were stratified by State according to the proportion of patients with breast cancer and private health insurance. We evaluated the possible treatment of first choice for patients with lymph-node-negative, estrogen-receptor-positive breast cancer, regardless of menopausal status. Interviewees were not aware of the objective of the study. Responses permitted a quantitative assessment of the care patterns regarding use of different chemotherapy regimens, type of premedication, use of growth factors, and use of intravenous antibiotics for febrile neutropenia. We calculated medication costs using the manufacturer's recommended prices. Other direct medical expenses, indirect medical costs, and non-medical costs were not included. RESULTS: Considering a hypothetical cohort of 100 patients without access to the 21-gene expression assay, the survey showed that 84 patients would receive chemotherapy. Reclassifying patient eligibility for chemotherapy according to the 21-gene expression assay would lower this number to 49. For a hypothetical cohort of 100 patients with access to the test, US$ 79,361.43 would be saved in main direct medical costs. Such results, however, would greatly vary according to tumor size: the 21-gene expression assay could increase direct medical costs in T1 tumors, and decrease costs in cases with T >2 cm. CONCLUSION: Considering the current price for the 21-gene expression assay in Brazil, our economic analysis suggests that such testing is an overall cost-saving, from the perspective of third party payers. Further, optimal use of resources would entail targeted use of the 21-gene expression assay.

Metastatic Biphasic Primitive Tumor in the Mandible of a Child.

Pediatric mandibular tumors present an aggressive biological behavior and difficult diagnosis. A wide range of odontogenic and nonodontogenic tumors comprise the spectrum of these lesions. We report a case of a 1-year-old male child patient showing facial asymmetry symptomatic of an expansive lesion extending throughout the body and ramus of the left hemimandible with a diameter of 8 cm. The histopathological report suggested a high-grade mucoepidermoid carcinoma (MEC), recommending further immunohistochemical investigation of the ectomesenchymal or neuroectodermal origin of the tumor cells. The patient evolved with extensive bilateral pleural effusion followed by metastasis in the middle third of the right humerus, and died 2 months after the first biopsy procedure by acute renal failure with tubular necrosis, before a final inconclusive immunohistochemical report was reached. The lack of resources for less-favored regions of Brazil impairs rapid biomolecular examinations such as immunohistochemical resulting in delay of appropriate therapeutic procedures.

Benign cervical schwannoma with tracheal invasion

ABSTRACT Schwannomas commonly develop in the cervical region, 25% - 45% of cases are diagnosed in this anatomical region. Tracheal neurogenic tumors are exceedingly rare and can be misdiagnosed as invasive thyroid carcinomas or other infiltrating malignancies when present at the level of the thyroid gland. Here, we present a case of synchronous benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma in a patient who was initially hospitalized for COVID-19. The patient presented with dyspnea that was later found to be caused by tracheal extension of a cervical tumor. Surgical excision was performed, and the surgical team proceeded with segmental tracheal resection, removal of the cervical mass, and total thyroidectomy. The specimen was sent for pathological analysis, which revealed synchronous findings of a benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma. The literature on this subject, together with the present case report, suggests that neurogenic tumors should be included in the differential diagnosis of obstructing tracheal cervical masses. Surgical excision is the first-line of treatment for benign cervical schwannomas.

L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion.

BACKGROUND: Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. MATERIALS AND METHODS: We studied 47 consecutive patients aged 37-88 (61.34±10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. RESULTS: LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. CONCLUSIONS: L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.

Lymphocyte-predominant triple-negative breast carcinomas in premenopausal patients: Lower expression of basal immunohistochemical markers.

OBJECTIVES: Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that they can benefit from immunotherapies. We selected 116 consecutive premenopausal patients with TNBC to compare the immunohistochemical profile of the group rich in tumor-infiltrating lymphocytes with those without this characteristic. MATERIALS AND METHODS: We reviewed all the original histological sections to assess pathological features, and to select a representative area for tissue microarrays and immunohistochemical study. Estrogen and progesterone receptors, HER2 and Ki-67 were evaluated in whole histological sections. The following markers were analyzed in tissue microarrays sections: androgen receptor, cytokeratin 5/6, cytokeratin 14, epidermal growth factor receptor (EGFR), vimentin, p16, claudin-3, -4, and -7, p63, and aldehyde dehydrogenase isoform 1 (ALDH1). Lymphocyte-predominant breast cancer (LPBC) was defined by the presence of more than 50% of lymphocytes in the intratumoral stroma. RESULTS: Twenty-six (22.4%) patients present tumors classified as LPBC and 90 (77.6%) as non-LPBC. The two groups were similar regarding age of patients, tumor grade and Ki-67 positive cells. LPBC cases presented lower frequency of expression of the basal cytokeratins, EGFR, and basal-like immunoprofile. There was a trend to higher expression of ALDH1 by stromal intratumoral cells. The expression of all other markers were similar in the two groups. CONCLUSIONS: Lymphocyte-predominant TNBC in premenopausal patients are mostly of non-basal phenotype.

Histogenesis of the acquired cystic kidney disease: an immunohistochemical study.

The aim of this study was to characterize by immunohistochemistry the histogenesis of cysts in acquired cystic kidney disease (ACKD). Thirty renal tissues fixed in 10% formalin and embedded in paraffin from 20 cases of ACKD were studied. Vimentin was used to stain the Bowman's capsule epithelium, Lotus tetragonolobus agglutinin (LTA) and Leu M1 (CD15) for proximal tubules; Tamm-Horsfall protein (THP) for distal tubules; epithelial membrane antigen (EMA), cytokeratin 19 (CK19), Arachis hypogea agglutinin (PNA), and Glycine maximum agglutinin (SBA) for distal tubules and collecting ducts; and Ulex europaeus agglutinin (UEA-I) and Dolichos biflorus agglutinin (DBA) for collecting ducts. A histologically normal kidney, free of cystic disease, was used as a control for all the markers. Most of the cysts showed strong reactivity to LTA and CD15, an immunophenotype more characteristic of proximal tubules.

Matrix metalloproteinase-9 expression in pterygium.

PURPOSE: To assess matrix metalloproteinase (MMP)-9 expression in pterygium lesion. METHODS: A prospective randomized clinical trial was done to evaluate the expression of matrix metalloproteinase in normal and in primary or recurrent pterygia in Tenon's capsule by immunohistochemical analysis and a computerized image analysis system. The data were submitted to statistical analysis. RESULTS: Matrix metalloproteinase expression showed no difference in normal Tenon's capsule and in primary or recurrent pterygia. CONCLUSION: The similar expression of the matrix metalloproteinase in normal Tenon's capsule and in primary or recurrent pterygia allowed us to conclude that matrix metalloproteinase is not implicated in the genesis or the recurrence of pterygium lesion.

The Apocrine Profile of Triple-negative Breast Carcinomas in Patients Aged 45 Years or Younger: favorable but rare features.

Objective Triple-negative breast carcinomas (TNBCs) represent a heterogeneous group of neoplasias, even though they generally exhibit a clinically more aggressive phenotype, and are more prevalent in young women. To date, targeted therapies for this group of tumors have not been defined. The aim of this study was to evaluate the frequency of the apocrine subtype in TBNCs from premenopausal patients as defined by the immunohistochemical expression of the androgen receptor (AR) and its association with: histological type; tumor grade; proliferative activity; epidermal growth factor receptor (EGFR) expression; and a basal-like phenotype. Methods A total of 118 tumor samples from patients aged 45 years or younger were selected and reviewed according to histological type and grade. Ki-67 expression was also evaluated. Immunohistochemical expression of the AR, basal cytokeratin ⅚, and EGFR expression were analyzed in tissue microarrays. The apocrine subset was defined by AR-positive expression. The basal-like phenotype was characterized by cytokeratin ⅚ and/or EGFR expression. Results An apocrine profile was identified in 6/118 (5.1%) cases. This subset of cases also exhibited a lower rate of Ki-67 expression (17.5% versus 70.0%, p = 0.02), and a trend toward a lower histological grade (66.7% versus 27.9%, p = 0.06). Conclusions The apocrine subtype of TNBCs is rare among premenopausal women, and it tends to present as carcinomas of lower grade and lower proliferative activity, suggesting a less aggressive biological phenotype.

[Isolated Richter's syndrome in central nervous system: case report].

Diffuse large cell non Hodgkin's lymphoma associated with chronic lymphoid leukemia (CLL), or Richter's syndrome, is a rare and serious complication. Isolated Richter's syndrome in the central nervous system is very rare; only 12 cases have been reported. We describe a 74-year-old patient with diffuse large cell non Hodgkin's lymphoma in the right frontal region with the appearance of multiform glioblastoma.

Loss of PTEN expression and AKT activation in HER2-positive breast carcinomas.

PURPOSE: To examine the expression of AKT and PTEN in a series of HER2-positive primary invasive breast tumors using immunohistochemistry, and to associate these expression profiles with classic pathologic features such as tumor grade, hormone receptor expression, lymphatic vascular invasion, and proliferation. METHODS: A total of 104 HER2-positive breast carcinoma specimens were prepared in tissue microarrays blocks for immunohistochemical detection of PTEN and phosphorylated AKT (pAKT). Original histologic sections were reviewed to assess pathological features, including HER2 status and Ki-67 index values. The associations between categorical and numeric variables were identified using Pearson's chi-square test and the Mann-Whitney, respectively. RESULTS: Co-expression of pAKT and PTEN was presented in 59 (56.7%) cases. Reduced levels of PTEN expression were detected in 20 (19.2%) cases, and these 20 tumors had a lower Ki-67 index value. In contrast, tumors positive for pAKT expression [71 (68.3%)] were associated with a higher Ki-67 index value. CONCLUSION: A role for AKT in the proliferation of HER2-positive breast cancers was confirmed. However, immunohistochemical detection of PTEN expression did not correlate with an inhibition of cellular proliferation or control of AKT phosphorylation, suggesting other pathways in these mechanisms of control.